The DOI matches its Crossref record; 132 of the 132 references it cites were found in a registry or an index; none of the 132 sources its claims cite is checked for support yet.
Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics
Open accessAbstract
Fragile X syndrome (FXS) is the most frequent form of inherited intellectual disability and is also linked to other neurologic and psychiatric disorders.FXS is caused by a triplet expansion that inhibits expression of the FMR1 gene; the gene product, FMRP, regulates mRNA metabolism in the brain and thus controls the expression of key molecules involved in receptor signaling and spine morphology.While there is no definitive cure for FXS, the understanding of FMRP function has paved the way for rational treatment designs that could potentially reverse many of the neurobiological changes observed in FXS.Additionally, behavioral, pharmacological, and cognitive interventions can raise the quality of life for both patients and their families.Conflict of interest: Randi Hagerman has received grant support from Roche, Novartis, Seaside Therapeutics, Forest, and Curemark to carry out clinical trials for fragile X and/or ASD.She has also consulted with Novartis regarding clinical trials in fragile X syndrome.Giovanni
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
0 of 132 cited sources checked · 0 supported · 0 flagged
In the paper
“FMR1 silencing is the consequence of rather complex epigenetic modifications (13).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
What the sources say
- Not checked yetcites [13] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“The risk of a PM to FM transition depends on the CGG repeat size, such that the expansion risk is nearly 100% for alleles of >99 CGG repeats (11).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
What the sources say
- Not checked yetcites [11] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“A recent study (12) showed that the number of AGG interruptions present in the CGG repeats correlates inversely with the risk of expansion to a FM in the next generation.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
What the sources say
- Not checked yetcites [12] Yrigollen, 2012, Genet Med. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“In FXS, cytosines located approximately up to 1-kb upstream of the CGG repeat sequences, including the FMR1 promoter, are methylated (14,15).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The presence of AGG interruptions, in addition to the CGG length, may thus better define the risk for transmission from a maternal PM to FM in the offspring.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Expansion from a PM to FM can occur with alleles as small as 56 CGGs (10).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
What the sources say
- Not checked yetcites [10] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Cytogenetic methods (6) used in the past to diagnose FXS have been replaced by molecular diagnostic of FMR1 DNA using Southern blot analysis and, more recently, PCR.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
What the sources say
- Not checked yetcites [6] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“PM alleles are unstable and have a strong tendency to expand to FM alleles upon maternal transmission.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Alleles possessing between 45 and 54 CGG repeats, referred to as gray-zone or intermediate alleles, are proposed to be precursors of PM alleles, potentially due to paternal and maternal meiotic instability (11).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
What the sources say
- Not checked yetcites [11] source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Fragile X syndrome (FXS), an X-linked condition first described by Martin and Bell (1), is the leading cause of inherited intellectual disability (ID).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
What the sources say
- Not checked yetcites [1] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- It may state two separate claims as one. 52
- Probably not a substantial claim. 7
- The quote only partly states this claim. 1
None of the sources cited for this claim have been checked yet.
In the paper
“Identified in 1991 by positional cloning (8), the FMR1 gene is characterized by the presence of a polymorphic CGG triplet sequence in the 5′ UTR (8, 9).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Due to compensation by the unaffected X chromosome, only one-third of female carriers with a full mutation (FM) have ID; the majority have normal IQ, although learning difficulties and emotional problems are common (7).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
What the sources say
- Not checked yetcites [7] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Normal alleles have a number of CGG repeats, ranging from 5 to 54, with a mode of 30.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Expansion in this triplet sequence gives rise to FXS, which is the prototype of unstable triplet expansion disorders.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“This boundary is missing in FM alleles, and the cytosines upstream of the CGG repeat become methylated around the thirteenth week of embryonic development (16).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
What the sources say
- Not checked yetcites [16] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Normal alleles are also methylated in the FMR1 promoter region but not in close proximity to the CGG repeat, which seems to be a “boundary” in the normal allele that prevents methylation from spreading.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Estimates report that FXS affects approximately 1 in 2,500 to 5,000 men and 1 in 4,000 to 6,000 women (2, 3).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“FXS is caused by mutations in the FMR1 gene, which is located on the X chromosome and whose locus at Xq27.3 coincides with the folate-sensitive fragile site (4, 5).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
What the sources say
- Not checked yetcites [4] Fryns, 1984, Acta Paediatr Scand Suppl.
- Not checked yetcites [5] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Premutation (PM) alleles have a number of CGG repeats, ranging from 55 to 200.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“FMRP has been detected in P bodies and stress granules as well, where it forms translationally silent preinitiation complexes (64) (Figure 2).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Figure 1
What the sources say
- Not checked yetcites [64] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These epigenetic changes promote a heterochromatic configuration that excludes the binding of specific transcription factors (19), thus turning gene expression off (20).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“High-throughput screenings supported by accompanying small scale studies have revealed that a wide array of neuronal mRNAs, with a large proportion encoding for presynaptic and postsynaptic proteins, is deregulated in the absence of FMRP, suggesting that concerted alteration of many proteins contributes to the FXS phenotype (62).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Figure 2
What the sources say
- Not checked yetcites [62] De Rubeis, 2012, Adv Exp Med Biol. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“In addition to altered methylation status, FXS alleles show deacetylation of histones H3 and H4, reduced methylation of lysine 4 (K4), and increased methylation of lysine 9 (K9) on histone H3 (18).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
What the sources say
- Not checked yetcites [18] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Of note, some alleles remain partially or even fully unmethylated (UFM), despite containing >200 CGG repeats, but the differences in methylation status are poorly understood.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The behavior of boys with FXS typically includes attention deficit hyperactivity disorder (ADHD), with significant impulsivity and anxiety, as well as behaviors that include repetitive language, hand biting, hand stereotypies, rocking, and sometimes head banging (24,25).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Early diagnosis.
What the sources say
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A child with FXS is often described as hyperaroused; an imbalance of the excitatory and inhibitory synaptic pathways described in the “From RNA metabolism to synaptic receptor dysfunction” section may contribute to such a clinical phenotype.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Early diagnosis.
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“FMRP is an RNA-binding protein, and, despite its clear shuttling from the nucleus to the cytoplasm (59,60), only the cytoplasmic function of FMRP has been well characterized.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Figure 1
Strength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“acetylation of histones H3 and H4 and methylation of lysine 9 on H3 of UFM alleles are more similar to those of FM alleles, while the level of methylation of lysines 4 and 27 on H3 are more similar to that of normal alleles (18,22).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“PM prevalence was found to be different in various ethnic groups; it was higher in people of mixed European descent compared with that in African American and Hispanic people (for both males and females) and shows a higher incidence for PM compared with that in previous studies (34,35).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Screening for FXS alleles: early diagnosis
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“FMRP regulates stability, subcellular transport, and translation of neuronal mRNAs encoding for proteins involved the in synaptic structure and function (58,(65)(66)(67).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Figure 1
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The fragile X mutation is the most common single genetic cause of autism, occurring in 1% to 6% of boys with ASD (7).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Clinical crosstalk between fragile X and autism
What the sources say
- Not checked yetcites [7] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Among the recurrent problems that may occur in children before 2 years of age are hypotonia, delayed motor milestones, hand flapping, poor eye contact, frequent emesis and/or otitis media, and irritability.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Early diagnosis.
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In addition, the majority of women with FM often do not have ID, and they are frequently diagnosed with FM following the diagnosis of FXS in their children.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Late diagnosis.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“As a consequence, gene transcription is inhibited, leading to the absence of its protein product FMRP (17).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Genetics of fragile X
What the sources say
- Not checked yetcites [17] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The results of a pilot newborn screening (NBS) study for FXS in the United States, based on the screening of 11,217 newborns, indicated that the observed prevalence of a PM allele is 1:188 in females and 1:480 in males, while the prevalence of gray-zone alleles (45-54 CGG repeats) is 1:70 in females and 1:107 in males (33).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Screening for FXS alleles: early diagnosis
What the sources say
- Not checked yetcites [33] Tassone F, et al. Newborn screening in fragile X syndrome: prevalence and allele distribution of the FMR1 gene. Paper presented at: American College of Medical Genetics Annual Clinical Genetics Meeting; July 26, 2012; Charlotte, North Carolina, USA. http://www.fragilex.org/community/international-fragile-x-conference/miami2012/agenda/ . Accessed October 19, 2012.
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“FXTAS (Figure 1) has been reported to affect approximately 46% of male and 17% of female adult carriers (28).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Early diagnosis.
What the sources say
- Not checked yetcites [28] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Approximately 30% of boys with FXS meet the diagnostic criteria for autism, and these children have the lowest developmental and adaptive behavior scores of those with FXS.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Early diagnosis.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“A late diagnosis may occur for older patients who may have undergone genetic testing prior to the 1991 discovery of the FMR1 gene (8) or for patients that carry a mild form of the disease, showing atypical symptoms as often occurs for the UFM alleles.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Late diagnosis.
What the sources say
- Not checked yetcites [8] source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“effects on other methylated genes cannot be excluded.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Epigenetic modulators.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Recently, the striatal enriched protein tyrosine phosphatase (STEP) has been shown to be upregulated in FXS, and genetic reduction of STEP diminished seizures and restored selected social and nonsocial anxiety-related behaviors in the Fmr1 KO mice (94).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Amelioration of the phenotype in the mouse model: a genetic approach
What the sources say
- Not checked yetcites [94] Goebel-Goody, 2012, Genes Brain Behav. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“While the action of 5-azadC appears to be specific in the context of the FMR1 gene, as shown by its lack of effect on the methylated sequence upstream of the FMR1 boundary (G.Neri, unpublished observations), effects on other methylated genes cannot be excluded.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Epigenetic modulators.
What the sources say
- Not checked yetcites G.Neri, unpublished observations
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe quote only partly states this claim.
None of the sources cited for this claim have been checked yet.
In the paper
“The molecular signaling pathways orchestrating protein synthesis, spine shape, and synaptic plasticity, such as mTOR and ERK (Figure 2), are also impaired in FXS (72,(87)(88)(89), possibly because some FMRP target mRNAs encode members of second messenger cascades converging on ERK (88,89).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Figure 2
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Moreover, it is presumed to be effective only on dividing cells, which excludes postmitotic neurons.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Epigenetic modulators.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
- The authors state this as an assumption: 5-aza-deoxycytidine is effective only on dividing cells, so it would not act on postmitotic neurons.
In the paper
“A significant amelioration of the hyperactivity and adaptive behavior of drug-treated boys (compared with those treated with placebo) was observed; however, the methylation state of FMR1 did not change, and the expression of the gene did not increase (100).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Epigenetic modulators.
What the sources say
- Not checked yetcites [100] Torrioli, 2008, Am J Med Genet A. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“This receptor unbalance results in enhanced mGluR-long-term depression (mGluR-LTD), the most commonly studied forms of hippocampal synaptic plasticity.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Figure 2
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Expression of a dominant-negative mutant of PAK in the forebrain of Fmr1 KO mice led to an improvement of several behavioral abnormalities, such as impaired locomotor activity, stereotypical anxiety, and trace fear conditioning, suggesting that the PAK signaling pathway could also represent a bona fide site for therapeutic intervention (93).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Amelioration of the phenotype in the mouse model: a genetic approach
What the sources say
- Not checked yetcites [93] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Reactivation was accompanied not only by DNA demethylation but also by changes in the epigenetic code of histones H3 and H4 (97).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Epigenetic modulators.
What the sources say
- Not checked yetcites [97] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Upon receptor activation, the FMRPmediated translational block is released, possibly due to changes (86) in its phosphorylation status, and protein synthesis can ensue.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Figure 2
What the sources say
- Not checked yetcites [86] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Because STEP acts on at least three molecules (ERK1/2, NMDA, and AMPA) affected in FXS, strategies to inhibit STEP activity may be considered for treating patients with FXS.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Amelioration of the phenotype in the mouse model: a genetic approach
What the sources say
- Not checked yetcites [94] Goebel-Goody, 2012, Genes Brain Behav. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“Because both mouse models have upregulated mTOR pathway activity, the authors propose that normal synaptic plasticity and cognition occur within an optimal range of mGluRmediated protein synthesis, such that deviations in either direction can lead to shared behavioral impairments.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Amelioration of the phenotype in the mouse model: a genetic approach
What the sources say
- Not checked yetcites [92] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Elevation of the glutamate receptors mGluR1 and mGluR5 and the reduced insertion of AMPA receptors into the postsynaptic membrane are two of the central mechanics of impaired synaptic plasticity in FXS: such a dysregulated signaling is the basis of mGluR theory (75).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Figure 2
What the sources say
- Not checked yetcites [75] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The strategy of restoring FMR1 gene activity, which is based on the presence of the intact FMR1 coding sequence, targets potentially reversible epigenetic changes, primarily DNA methylation.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Epigenetic modulators.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The FMR1 coding sequence remains intact in fragile X syndrome cells, so restoring gene activity is feasible.
None of the sources cited for this claim have been checked yet.
In the paper
“FMRP activity is regulated in response to metabotropic glutamate receptors (mGluRs) (78), 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid (AMPA) receptors (79), γ-aminobutyric acid (GABA) receptors (76,80,81), N-methyl-d-aspartate (NMDA) receptors (82)(83)(84), and the tyrosine kinase or BDNF/NT-3 growth factor (TrkB) receptors (85).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Figure 2
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Two possible approaches are presently being considered for a substantial treatment of FXS: (a) reactivation of the affected gene and (b) compensating for the lack of FMRP.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Therapeutic approaches to FXS
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because the mouse model recapitulates morphological changes and behavioral deficits seen in human patients, these molecular insights have led clinicians to design targeted treatments (see below).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Figure 2
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The Fmr1 knockout mouse model reproduces the morphological and behavioral features of human fragile X syndrome closely enough that molecular findings in it can guide targeted treatments for patients.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In the absence of FMRP, there is an increase in the synthesis of several proteins involved in cytoskeleton remodeling and receptor internalization (i.e., Arc) (Figure 2) as well as reduction of other proteins due to a reduced stability of their mRNAs (i.e., GABA-R subunits).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Figure 2
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The resulting 50% reduction in mGluR5 protein levels in the offspring led to the correction of typical FXS phenotypic features, including spine dysmorphogenesis and audiogenic seizures, and restored mGluR-LTD (90).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Amelioration of the phenotype in the mouse model: a genetic approach
What the sources say
- Not checked yetcites [90] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The GABA receptor system has also been reported as downregulated in FXS, partially due to destabilization of the mRNAs encoding the GABA receptor subunits (76,80,113).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Glutamatergic system.
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“No significant improvement in the primary outcome measure or in secondary measures of language, attention/executive function, or behavior was observed when compared with placebo, possibly due to the potency or dosage of CX516 used (105).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Glutamatergic system.
What the sources say
- Not checked yetcites [105] source
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Treatment of young mice with minocycline, a broad-spectrum antibiotic, had a dual effect: increased phosphorylation of GluR1 and subsequent membrane insertion of AMPA receptors (124)”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Glutamatergic system.
What the sources say
- Not checked yetcites [124] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Acamprosate, a molecule used to maintain abstinence from alcohol, is able to block NMDA-R as well as activate GABA A -R and was recently tested in three young adult patients with FXS, who showed global benefit (as rated by the CGI-I scale) and marked communication improvement (115).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Glutamatergic system.
What the sources say
- Not checked yetcites [115] source
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Treatment of Fmr1 KO mice with the mGluR antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) (Figure 3B) resulted in suppression of the audiogenic seizure phenotype (106) and rescue of dendritic spine morphology in the Fmr1 KO mouse (107).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Glutamatergic system.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“and mice demonstrated improvements in anxiety and in a cognitive task (125).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Glutamatergic system.
What the sources say
- Not checked yetcites [125] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The third tested compound is valproic acid (101), which is already known as a reactivator of silenced genes (102) that appeared to be a weak reactivator of FM (103).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Epigenetic modulators.
What the sources say
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Long term use of a similar mGluR5 antagonist, CTEC, in adult animals corrected elevated hippocampal LTD, protein synthesis, spine dysmorphogenesis, overactive ERK and mTOR signaling, and partially corrected macroorchidism (108).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Glutamatergic system.
What the sources say
- Not checked yetcites [108] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Fenobam, used in the past for anxiety treatment (109), was recently tested in adults with FXS (37).Beneficial effects such as reduced anxiety and hyperarousal, improved prepulse inhibition of startle, and better accuracy on a continuous performance task were also reported.”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Glutamatergic system.
What the sources say
- Not checked yetcites [37] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Intriguingly, in this small trial, improvements in inappropriate speech, stereotypic behavior, and hyperactivity and efficacy have been reported in adults with FXS who have a fully methylated FM allele but not in those with mosaicism (36).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Glutamatergic system.
What the sources say
- Not checked yetcites [36] Jacquemont, 2011, Sci Transl Med. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“FMRP is also required for neural stem and progenitor cell proliferation, differentiation, and survival, suggesting additional mechanisms that could explain certain features of the disease (136).”
§ Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics > Conclusions and perspectives
What the sources say
- Not checked yetcites [136] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
The Fmr1 knockout mouse model reproduces the morphological and behavioral features of human fragile X syndrome closely enough that molecular findings in it can guide targeted treatments for patients.
“Because the mouse model recapitulates morphological changes and behavioral deficits seen in human patients, these molecular insights have led clinicians to design targeted treatments (see below).”
The paper relies on this without support.
The FMR1 coding sequence remains intact in fragile X syndrome cells, so restoring gene activity is feasible.
“The strategy of restoring FMR1 gene activity, which is based on the presence of the intact FMR1 coding sequence, targets potentially reversible epigenetic changes, primarily DNA methylation.”
The authors state this as an assumption.
5-aza-deoxycytidine is effective only on dividing cells, so it would not act on postmitotic neurons.
“Moreover, it is presumed to be effective only on dividing cells, which excludes postmitotic neurons.”
The paper relies on this without support.
Modulating levels of dysregulated proteins can regulate impaired plasticity associated with FXS.
“Another approach to regulate impaired plasticity associated with FXS is to modulate the levels of dysregulated proteins.”
The paper relies on this without support.
FMRP functions in regulating mRNA metabolism in the brain.
“FMRP is largely established to function in regulating mRNA metabolism in brain.”
The paper relies on this without support.
Lack of FMRP causes dysregulated synthesis of synaptic molecules, including elevated levels of several proteins (Arc, αCAMKII, MMP9, GSK-3β, mGluR, NMDA) and reduced GABA and AMPA receptor activity.
“Lack of FMRP leads to a dysregulated synthesis of molecules with key functions at synapses, such as increased levels of Arc, αCAMKII, MMP9, GSK-3β, mGluR, and NMDA and decreased GABA and AMPA receptor activity.”
The paper relies on this without support.
The placebo effect observed in most drug-based trials is significant.
“the significant placebo effect observed in most drug-based trials”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“FXS is due to loss of function of the RNA-binding protein FMRP (Bagni et al., 2012, Bassell and Warren, 2008), which regulates dendritic targeting of mRNAs (Dictenberg et al., 2008) and controls protein synthesis and mRNA decay in neuronal soma and at synapses (Bassell and Warren, 2008).”
From CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation (2013) · cites this paper as Bagni et al., 2012
In the citing paper
“Fragile X syndrome is caused by expansion of a cytosine-guanine-guanine (CGG) trinucleotide in the promoter of the fragile X mental retardation (FMR1) gene or, more rarely, due to point mutations [18].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [18]
In the citing paper
“The expansion of the CGG repeat over 200 copies leads to the transcriptional silencing of the gene and loss of the fragile X mental retardation protein (FMRP).”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [18]
In the citing paper
“FMRP is an RNA-binding protein known to interact with specific mRNAs in the brain and regulate synaptic plasticity-dependent local protein synthesis [18, 80, 275].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [18]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Normal and intermediate allele ranges overlap
MinorThe paper assigns 45-54 CGG repeats to both normal alleles and gray-zone or intermediate alleles, leaving their classification inconsistent.
“Normal alleles have a number of CGG repeats, ranging from 5 to 54, with a mode of 30.”
“Alleles possessing between 45 and 54 CGG repeats, referred to as gray-zone or intermediate alleles, are proposed to be precursors of PM alleles”
Citations
Cites
Verkerk, A. J. M. H., Pieretti, M., Sutcliffe, J. S., Fu, Y.-H., Kuhl, D. P. A., Pizzuti, A., Reiner, O., Richards, S., Victoria, M. F., Zhang, F., et al. (1991) · Cell · doi:10.1016/0092-8674(91)90397-h · Cited by 3,481
Dawson, G., Rogers, S., Munson, J., Smith, M., Winter, J., Greenson, J., Donaldson, A., & Varley, J. (2010) · Pediatrics · doi:10.1542/peds.2009-0958 · Cited by 2,835
Fu, Y.-H., Kuhl, D. P. A., Pizzuti, A., Pieretti, M., Sutcliffe, J. S., Richards, S., Verkert, A. J. M. H., Holden, J. J. A., Fenwick, R. G., Warren, S. T., et al. (1991) · Cell · doi:10.1016/0092-8674(91)90283-5 · Cited by 2,080
FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism
Darnell, J. C., Van Driesche, S. J., Zhang, C., Hung, K. Y. S., Mele, A., Fraser, C. E., Stone, E. F., Chen, C., Fak, J. J., Chi, S. W., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.013 · Cited by 2,072
Phiel, C. J., Zhang, F., Huang, E. Y., Guenther, M. G., Lazar, M. A., & Klein, P. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101287200 · Cited by 1,758
The mGluR theory of fragile X mental retardation
Bear, M. F., Huber, K. M., & Warren, S. T. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.04.009 · Cited by 1,580
Instability of a 550-Base Pair DNA Segment and Abnormal Methylation in Fragile X Syndrome
Oberlé, I., Rousseau, F., Heitz, D., Kretz, C., Devys, D., Hanauer, A., Boué, J., Bertheas, M. F., & Mandel, J. L. (1991) · Science · doi:10.1126/science.252.5009.1097 · Cited by 1,499
Absence of expression of the FMR-1 gene in fragile X syndrome
Pieretti, M., Zhang, F., Fu, Y.-H., Warren, S. T., Oostra, B. A., Caskey, C. T., & Nelson, D. L. (1991) · Cell · doi:10.1016/0092-8674(91)90125-i · Cited by 1,476
Altered synaptic plasticity in a mouse model of fragile X mental retardation
Huber, K. M., Gallagher, S. M., Warren, S. T., & Bear, M. F. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122205699 · Cited by 1,349
Brown, V., Jin, P., Ceman, S., Darnell, J. C., O'Donnell, W. T., Tenenbaum, S. A., Jin, X., Feng, Y., Wilkinson, K. D., Keene, J. D., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00568-2 · Cited by 1,109
Fmr1 knockout mice: A model to study fragile X mental retardation
THEDUTCHBELGIANFRAGILEXCONSOR (1994) · Cell · doi:10.1016/0092-8674(94)90569-x · Cited by 1,108
Anderson, P., & Kedersha, N. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200512082 · Cited by 984
Correction of Fragile X Syndrome in Mice
Dölen, G., Osterweil, E., Rao, B. S. S., Smith, G. B., Auerbach, B. D., Chattarji, S., & Bear, M. F. (2007) · Neuron · doi:10.1016/j.neuron.2007.12.001 · Cited by 979
DNA methylation represses FMR-1 transcription in fragile X syndrome
Sutcliffe, J. S., Nelson, D. L., Zhang, F., Pieretti, M., Caskey, C. T., Saxe, D., & Warren, S. T. (1992) · Human Molecular Genetics · doi:10.1093/hmg/1.6.397 · Cited by 680
Zalfa, F., Giorgi, M., Primerano, B., Moro, A., Di Penta, A., Reis, S., Oostra, B., & Bagni, C. (2003) · Cell · doi:10.1016/s0092-8674(03)00079-5 · Cited by 676
Self-citationThe Fragile X Syndrome Protein Represses Activity-Dependent Translation through CYFIP1, a New 4E-BP
Napoli, I., Mercaldo, V., Boyl, P. P., Eleuteri, B., Zalfa, F., De Rubeis, S., Di Marino, D., Mohr, E., Massimi, M., Falconi, M., et al. (2008) · Cell · doi:10.1016/j.cell.2008.07.031 · Cited by 609
Self-citationJacquemont, S., Curie, A., des Portes, V., Torrioli, M. G., Berry-Kravis, E., Hagerman, R. J., Ramos, F. J., Cornish, K., He, Y., Paulding, C., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3001708 · Cited by 609
Self-citationMutations causing syndromic autism define an axis of synaptic pathophysiology
Auerbach, B. D., Osterweil, E. K., & Bear, M. F. (2011) · Nature · doi:10.1038/nature10658 · Cited by 592
(1994) · PubMed · Cited by 565
Dysregulation of mTOR signaling in fragile X syndrome
Sharma, A., Hoeffer, C. A., Takayasu, Y., Miyawaki, T., McBride, S. M., Klann, E., & Zukin, R. S. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3696-09.2010 · Cited by 557
Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP
Yan, Q. J., Rammal, M., Tranfaglia, M., & Bauchwitz, R. P. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.06.004 · Cited by 521
RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice
Miyashiro, K. Y., Beckel-Mitchener, A., Purk, T. P., Becker, K. G., Barret, T., Liu, L., Carbonetto, S., Weiler, I. J., Greenough, W. T., & Eberwine, J. (2003) · Neuron · doi:10.1016/s0896-6273(03)00034-5 · Cited by 495
Chronic Pharmacological mGlu5 Inhibition Corrects Fragile X in Adult Mice
Michalon, A., Sidorov, M., Ballard, T. M., Ozmen, L., Spooren, W., Wettstein, J. G., Jaeschke, G., Bear, M. F., & Lindemann, L. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.009 · Cited by 489
A PEDIGREE OF MENTAL DEFECT SHOWING SEX-LINKAGE
Martin, J. P., & Bell, J. (1943) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.6.3-4.154 · Cited by 481
From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome
Bagni, C., & Greenough, W. T. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1667 · Cited by 475
Self-citationBilousova, T. V., Dansie, L., Ngo, M., Aye, J., Charles, J. R., Ethell, D. W., & Ethell, I. M. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2008.061796 · Cited by 465
Incidence of Fragile X Syndrome by Newborn Screening for Methylated FMR1 DNA
Coffee, B., Keith, K., Albizua, I., Malone, T., Mowrey, J., Sherman, S. L., & Warren, S. T. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.09.007 · Cited by 436
Leblond, C. S., Heinrich, J., Delorme, R., Proepper, C., Betancur, C., Huguet, G., Konyukh, M., Chaste, P., Ey, E., Rastam, M., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002521 · Cited by 429
Muddashetty, R. S., Kelić, S., Gross, C., Xu, M., & Bassell, G. J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.0937-07.2007 · Cited by 421
Expansion of the Fragile X CGG Repeat in Females with Premutation or Intermediate Alleles
Nolin, S. L., Brown, W. T., Glicksman, A., Houck, Jr., Gargano, A. D., Sullivan, A., Biancalana, V., Bröndum-Nielsen, K., Hjalgrim, H., Holinski-Feder, E., et al. (2003) · The American Journal of Human Genetics · doi:10.1086/367713 · Cited by 421
A pilot open label, single dose trial of fenobam in adults with fragile X syndrome
Berry-Kravis, E., Hessl, D., Coffey, S., Hervey, C., Schneider, A., Yuhas, J., Hutchison, J., Snape, M., Tranfaglia, M., Nguyen, D. V., et al. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2008.063701 · Cited by 411
Self-citationEberhart, D. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.8.1083 · Cited by 390
A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability
Zalfa, F., Eleuteri, B., Dickson, K. S., Mercaldo, V., Rubeis, S. D., di Penta, A., Tabolacci, E., Chiurazzi, P., Neri, G., Grant, S. G. N., et al. (2007) · Nature Neuroscience · doi:10.1038/nn1893 · Cited by 370
Self-citationAutistic behavior in children with fragile X syndrome: Prevalence, stability, and the impact of FMRP
Hatton, D. D., Sideris, J., Skinner, M., Mankowski, J., Bailey, D. B., Roberts, J., & Mirrett, P. (2006) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31286 · Cited by 359
Tassone, F., Pan, R., Amiri, K. M. A., Taylor, A. K., & Hagerman, P. J. (2007) · Journal of Molecular Diagnostics · doi:10.2353/jmoldx.2008.070073 · Cited by 350
Self-citationValproate Induces Replication-independent Active DNA Demethylation
Detich, N., Bovenzi, V., & Szyf, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303740200 · Cited by 345
Berry-Kravis, E. M., Hessl, D., Rathmell, B., Zarevics, P., Cherubini, M., Walton-Bowen, K., Mu, Y., Nguyen, D. V., Gonzalez-Heydrich, J., Wang, P. P., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004214 · Cited by 328
Self-citationAcetylated histones are associated with FMR1 in normal but not fragile X-syndrome cells
Coffee, B., Zhang, F., Warren, S. T., & Reines, D. (1999) · Nature Genetics · doi:10.1038/8807 · Cited by 325
Decreased expression of the GABAA receptor in fragile X syndrome
D'Hulst, C., De Geest, N., Reeve, S. P., Van Dam, D., De Deyn, P. P., Hassan, B. A., & Kooy, R. F. (2006) · Brain Research · doi:10.1016/j.brainres.2006.08.115 · Cited by 318
Cordeiro, L., Ballinger, E., Hagerman, R., & Hessl, D. (2011) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-010-9067-y · Cited by 316
Self-citationOlmos-Serrano, J. L., Paluszkiewicz, S. M., Martin, B. S., Kaufmann, W. E., Corbin, J. G., & Huntsman, M. M. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1714-10.2010 · Cited by 309
Restivo, L., Ferrari, F., Passino, E., Sgobio, C., Bock, J., Oostra, B. A., Bagni, C., & Ammassari-Teule, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504984102 · Cited by 299
Self-citationFMRP Mediates mGluR5-Dependent Translation of Amyloid Precursor Protein
Westmark, C. J., & Malter, J. S. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050052 · Cited by 296 · cited 1×
“Interestingly, the amyloid β -protein precursor (A β PP) is upregulated in the FXS mouse model (52, 73).”
Dombrowski, C. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.4.371 · Cited by 289
Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice
Hayashi, M. L., Rao, B. S. S., Seo, J.-S., Choi, H.-S., Dolan, B. M., Choi, S.-Y., Chattarji, S., & Tonegawa, S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705003104 · Cited by 281
Filipovic-Sadic, S., Sah, S., Chen, L., Krosting, J., Sekinger, E. A., Zhang, W., Hagerman, P. J., Stenzel, T. T., Hadd, A. G., Latham, G. J., et al. (2010) · Clinical Chemistry · doi:10.1373/clinchem.2009.136101 · Cited by 280
Self-citationNishimura, Y., Martin, C. L., Vazquez-Lopez, A., Spence, S. J., Alvarez-Retuerto, A. I., Sigman, M., Steindler, C., Pellegrini, S., Schanen, N. C., Warren, S. T., et al. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm116 · Cited by 276
Epilepsy in fragile X syndrome
Berry‐Kravis, E. (2002) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2002.tb00277.x · Cited by 271
Nakamoto, M., Nalavadi, V., Epstein, M. P., Narayanan, U., Bassell, G. J., & Warren, S. T. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707484104 · Cited by 245
Narayanan, U., Nalavadi, V., Nakamoto, M., Pallas, D. C., Ceman, S., Bassell, G. J., & Warren, S. T. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2969-07.2007 · Cited by 228
Open-label add-on treatment trial of minocycline in fragile X syndrome.
Paribello, C., Tao, L., Folino, A., Berry-Kravis, E., Tranfaglia, M., Ethell, I. M., & Ethell, D. W. (2010) · BMC Neurology · doi:10.1186/1471-2377-10-91 · Cited by 223
Downregulation of Tonic GABAergic Inhibition in a Mouse Model of Fragile X Syndrome
Curia, G., Papouin, T., Séguéla, P., & Avoli, M. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhn159 · Cited by 218
Chiurazzi, P., Grazia Pomponi, M., Pietrobono, R., Bakker, C. E., Neri, G., & Oostra, B. A. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.12.2317 · Cited by 217
Self-citationNarayanan, U., Nalavadi, V., Nakamoto, M., Thomas, G., Ceman, S., Bassell, G. J., & Warren, S. T. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.c800055200 · Cited by 216
Open-Label Treatment Trial of Lithium to Target the Underlying Defect in Fragile X Syndrome
Berry-Kravis, E., Sumis, A., Hervey, C., Nelson, M., Porges, S. W., Weng, N., Weiler, I. J., & Greenough, W. T. (2008) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0b013e31817dc447 · Cited by 215
Fernandez-Carvajal, I., Walichiewicz, P., Xiaosen, X., Pan, R., Hagerman, P. J., & Tassone, F. (2009) · The Journal of Molecular Diagnostics · doi:10.2353/jmoldx.2009.080173 · Cited by 204
Self-citationGatto (2010) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2010.00004 · Cited by 204
Hessl, D., Dyer-Friedman, J., Glaser, B., Wisbeck, J., Barajas, R. G., Taylor, A., & Reiss, A. L. (2001) · Pediatrics · doi:10.1542/peds.108.5.e88 · Cited by 201
Sittler, A., Devys, D., Weber, C., & Mandel, J.-L. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.1.95 · Cited by 198
In Vitro Reactivation of the FMR1 Gene Involved in Fragile X Syndrome
Chiurazzi, P., Pomponi, M. G., Willemsen, R., Oostra, B. A., & Neri, G. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.1.109 · Cited by 198
Self-citationAltered mTOR signaling and enhanced CYFIP2 expression levels in subjects with fragile X syndrome
Hoeffer, C. A., Sanchez, E., Hagerman, R. J., Mu, Y., Nguyen, D. V., Wong, H., Whelan, A. M., Zukin, R. S., Klann, E., & Tassone, F. (2012) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2012.00768.x · Cited by 198
Self-citationCharacterization of the full fragile X syndrome mutation in fetal gametes
Malter, H. E., Iber, J. C., Willemsen, R., Graaff, E. D., Tarleton, J. C., Leisti, J., Warren, S. T., & Oostra, B. A. (1997) · Nature Genetics · doi:10.1038/ng0297-165 · Cited by 197
Meredith, R. M., Holmgren, C. D., Weidum, M., Burnashev, N., & Mansvelder, H. D. (2007) · Neuron · doi:10.1016/j.neuron.2007.04.028 · Cited by 190
AGG interruptions within the maternal FMR1 gene reduce the risk of offspring with fragile X syndrome
Yrigollen, C. M., Durbin-Johnson, B., Gane, L., Nelson, D. L., Hagerman, R., Hagerman, P. J., & Tassone, F. (2012) · Genetics in Medicine · doi:10.1038/gim.2012.34 · Cited by 179
Self-citationNormal phenotype in two brothers with a full FMR1 mutation
Smeets, H. J. M., Smits, A. P. T., Verheij, C. E., Theelen, J. P. G., Willemsen, R., Burgt, I. V. D., Hoogeveen, A. T., Oosterwijk, J. C., & Oostra, B. A. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.11.2103 · Cited by 179
No Change in the Age of Diagnosis for Fragile X Syndrome: Findings From a National Parent Survey
Bailey, D. B., Raspa, M., Bishop, E., & Holiday, D. (2009) · Pediatrics · doi:10.1542/peds.2008-2992 · Cited by 175
Bacalman, S., Farzin, F., Bourgeois, J. A., Cogswell, J., Goodlin-Jones, B. L., Gane, L. W., Grigsby, J., Leehey, M. A., Tassone, F., & Hagerman, R. J. (2006) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v67n0112 · Cited by 175
Self-citationADHD symptoms in children with FXS
Sullivan, K., Hatton, D., Hammer, J., Sideris, J., Hooper, S., Ornstein, P., & Bailey, D. (2006) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31388 · Cited by 174
Abnormal Striatal GABA Transmission in the Mouse Model for the Fragile X Syndrome
Centonze, D., Rossi, S., Mercaldo, V., Napoli, I., Ciotti, M. T., De Chiara, V., Musella, A., Prosperetti, C., Calabresi, P., Bernardi, G., et al. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.09.008 · Cited by 171
Self-citationPecknold, J. C., McClure, D., APPELTAUER, L., Wrzesinski, L., & ALLAN, T. (1982) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-198204000-00010 · Cited by 165
Expansion of an FMR1 Grey-Zone Allele to a Full Mutation in Two Generations
Fernandez-Carvajal, I., Lopez Posadas, B., Pan, R., Raske, C., Hagerman, P. J., & Tassone, F. (2009) · The Journal of Molecular Diagnostics · doi:10.2353/jmoldx.2009.080174 · Cited by 164
Self-citationChen, L., Yun, S.-W., Seto, J., Liu, W., & Toth, M. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00406-8 · Cited by 160
Berry-Kravis, E., Krause, S. E., Block, S. S., Guter, S., Wuu, J., Leurgans, S., Decle, P., Potanos, K., Cook, E., Salt, J., et al. (2006) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2006.16.525 · Cited by 155
Self-citationThe emerging fragile X premutation phenotype: Evidence from the domain of social cognition
Cornish, K., Kogan, C., Turk, J., Manly, T., James, N., Mills, A., & Dalton, A. (2005) · Brain and Cognition · doi:10.1016/j.bandc.2004.08.020 · Cited by 148
Min, W. W., Yuskaitis, C. J., Yan, Q., Sikorski, C., Chen, S., Jope, R. S., & Bauchwitz, R. P. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.09.017 · Cited by 146
Deregulation of EIF4E: a novel mechanism for autism
Neves-Pereira, M., Müller, B., Massie, D., Williams, J. H. G., O’Brien, P. C. M., Hughes, A., Shen, S.-B., Clair, D. S., & Miedzybrodzka, Z. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2009.066852 · Cited by 142
Suvrathan, A., Hoeffer, C. A., Wong, H., Klann, E., & Chattarji, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002262107 · Cited by 137
Advances in understanding the molecular basis of FXTAS
Garcia-Arocena, D., & Hagerman, P. J. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq166 · Cited by 136
Pacey, L. K. K., Heximer, S. P., & Hampson, D. R. (2009) · Molecular Pharmacology · doi:10.1124/mol.109.056127 · Cited by 133
Molecular dissection of the events leading to inactivation of the FMR1 gene
Pietrobono, R., Tabolacci, E., Zalfa, F., Zito, I., Terracciano, A., Moscato, U., Bagni, C., Oostra, B., Chiurazzi, P., & Neri, G. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi024 · Cited by 130
Self-citationEvidence for multiple loci from a genome scan of autism kindreds
Schellenberg, G. D., Dawson, G., Sung, Y. J., Estes, A., Munson, J., Rosenthal, E., Rothstein, J., Flodman, P., Smith, M., Coon, H., et al. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001874 · Cited by 129
Nalavadi, V. C., Muddashetty, R. S., Gross, C., & Bassell, G. J. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5057-11.2012 · Cited by 128
New perspectives on the biology of fragile X syndrome
Wang, T., Bray, S. M., & Warren, S. T. (2012) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2012.02.002 · Cited by 116
Neurofibromatosis type 1 growth charts
Clementi, M., Milani, S., Mammi, I., Boni, S., Monciotti, C., & Tenconi, R. (1999) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19991203)87:4 · Cited by 111
Self-citationReversal of Fragile X Phenotypes by Manipulation of AβPP/Aβ Levels in Fmr1KO Mice
Westmark, C. J., Westmark, P. R., O'Riordan, K. J., Ray, B. C., Hervey, C. M., Salamat, M. S., Abozeid, S. H., Stein, K. M., Stodola, L. A., Tranfaglia, M., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026549 · Cited by 110
Chonchaiya, W., Au, J., Schneider, A., Hessl, D., Harris, S. W., Laird, M., Mu, Y., Tassone, F., Nguyen, D. V., & Hagerman, R. J. (2012) · Human Genetics · doi:10.1007/s00439-011-1106-6 · Cited by 109
Self-citationGenetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model
Goebel‐Goody, S. M., Wilson‐Wallis, E. D., Royston, S., Tagliatela, S. M., Naegele, J. R., & Lombroso, P. J. (2012) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2012.00781.x · Cited by 108
van der Zwaag, B., Staal, W. G., Hochstenbach, R., Poot, M., Spierenburg, H. A., de Jonge, M. V., Verbeek, N. E., van 't Slot, R., van Es, M. A., Staal, F. J., et al. (2010) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31055 · Cited by 108
Naumann, A., Hochstein, N., Weber, S., Fanning, E., & Doerfler, W. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.09.018 · Cited by 107
Utari, A., Chonchaiya, W., Rivera, S. M., Schneider, A., Hagerman, R. J., Faradz, S. M. H., Ethell, I. M., & Nguyen, D. V. (2010) · American Journal on Intellectual and Developmental Disabilities · doi:10.1352/1944-7558-115.5.433 · Cited by 105
Self-citationEadie, B. D., Cushman, J. D., Kannangara, T. S., Fanselow, M. S., & Christie, B. R. (2010) · Hippocampus · doi:10.1002/hipo.20890 · Cited by 103
McDuffie, A. S., Abbeduto, L., Lewis, P. F., Kover, S. T., Kim, J.-S., Weber, A., & Brown, W. T. (2010) · American Journal on Intellectual and Developmental Disabilities · doi:10.1352/1944-7558-115.4.307 · Cited by 101
Torrioli, M. G., Vernacotola, S., Peruzzi, L., Tabolacci, E., Mila, M., Militerni, R., Musumeci, S., Ramos, F. J., Frontera, M., Sorge, G., et al. (2008) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32268 · Cited by 100
Self-citationGenetic and Environmental Influences on the Cognitive Outcomes of Children With Fragile X Syndrome
DYER-FRIEDMAN, J., GLASER, B., HESSL, D., JOHNSTON, C., HUFFMAN, L. C., TAYLOR, A., WISBECK, J., & REISS, A. L. (2002) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200203000-00002 · Cited by 100
Bilousova, T. V., Rusakov, D. A., Ethell, D. W., & Ethell, I. M. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03701.x · Cited by 98
Yun, S. H., & Trommer, B. L. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22546 · Cited by 97
Aberrant early-phase ERK inactivation impedes neuronal function in fragile X syndrome
Kim, S. H., Markham, J. A., Weiler, I. J., & Greenough, W. T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800257105 · Cited by 97
Lyon, E., Laver, T. A., Yu, P., Jama, M., Young, K., Zoccoli, M. A., & Marlowe, N. (2010) · Journal of Molecular Diagnostics · doi:10.2353/jmoldx.2010.090229 · Cited by 95
BDNF and TrkB in neuronal differentiation of Fmr1-knockout mouse
Louhivuori, V., Vicario, A., Uutela, M., Rantamäki, T., Louhivuori, L. M., Ċastrén, E., Tongiorgi, E., Åkerman, K. E. O., & Castrén, M. L. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.10.018 · Cited by 93
Tabolacci, E., Pietrobono, R., Moscato, U., Oostra, B. A., Chiurazzi, P., & Neri, G. (2005) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201393 · Cited by 92
Self-citationInteraction of the Transcription Factors USF1, USF2, and α-Pal/Nrf-1 with the FMR1 Promoter
Kumari, D., & Usdin, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009629200 · Cited by 92
Epigenetic analysis reveals a euchromatic configuration in the FMR1 unmethylated full mutations
Tabolacci, E., Moscato, U., Zalfa, F., Bagni, C., Chiurazzi, P., & Neri, G. (2008) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.130 · Cited by 91
Self-citationFMR1 premutation and full mutation molecular mechanisms related to autism
Hagerman, R., Au, J., & Hagerman, P. (2011) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-011-9084-5 · Cited by 85
Self-citationDawson, G., Hessl, D. R., & Frey, K. S. (1994) · Development and Psychopathology · doi:10.1017/s0954579400004776 · Cited by 83
Su, T., Fan, H.-X., Jiang, T., Sun, W.-W., Den, W.-Y., Gao, M.-M., Chen, S.-Q., Zhao, Q.-H., & Yi, Y.-H. (2011) · Psychopharmacology · doi:10.1007/s00213-010-2130-2 · Cited by 76
Secondary medical diagnosis in fragile X syndrome with and without autism spectrum disorder
García‐Nonell, C., Ratera, E. R., Harris, S., Hessl, D., Ono, M. Y., Tartaglia, N., Marvin, E., Tassone, F., & Hagerman, R. J. (2008) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32290 · Cited by 76
Self-citationShang, Y., Wang, H., Mercaldo, V., Li, X., Chen, T., & Zhuo, M. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06314.x · Cited by 72
Lacoux, C., Marino, D. D., Boyl, P. P., Zalfa, F., Yan, B., Ciotti, M. T., Falconi, M., Urlaub, H., Achsel, T., Mougin, A., et al. (2012) · Nucleic Acids Research · doi:10.1093/nar/gkr1254 · Cited by 72
Self-citationTreatment with valproic acid ameliorates ADHD symptoms in fragile X syndrome boys
Torrioli, M., Vernacotola, S., Setini, C., Bevilacqua, F., Martinelli, D., Snape, M., Hutchison, J. A., Di Raimo, F. R., Tabolacci, E., & Neri, G. (2010) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33484 · Cited by 71
Self-citationBrief Report: Acamprosate in Fragile X Syndrome
Erickson, C. A., Mullett, J. E., & McDougle, C. J. (2010) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-010-0988-9 · Cited by 67
Origins of the fragile X syndrome mutation.
Hirst, M. C., Knight, S. J., Christodoulou, Z., Grewal, P. K., Fryns, J. P., & Davies, K. E. (1993) · Journal of Medical Genetics · doi:10.1136/jmg.30.8.647 · Cited by 53 · cited 1×
“Estimates report that FXS affects approximately 1 in 2,500 to 5,000 men and 1 in 4,000 to 6,000 women (2, 3).”
De Rubeis, S., Fernández, E., Buzzi, A., Di Marino, D., & Bagni, C. (2012) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-7091-0932-8_23 · Cited by 48
Self-citationTabolacci, E., De Pascalis, I., Accadia, M., Terracciano, A., Moscato, U., Chiurazzi, P., & Neri, G. (2008) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e32830500a1 · Cited by 44
Self-citationNeural plasticity, sensitive periods, and psychopathology
Cicchetti, D. (2015) · Development and Psychopathology · doi:10.1017/s0954579415000012 · Cited by 41
Heads‐up: New roles for the fragile X mental retardation protein in neural stem and progenitor cells
Callan, M. A., & Zarnescu, D. C. (2011) · genesis · doi:10.1002/dvg.20745 · Cited by 39
Turk, J. (2011) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e328349bb77 · Cited by 35
Behavioral Intervention for Problem Behavior in Children With Fragile X Syndrome
Moskowitz, L. J., Carr, E. G., & Durand, V. M. (2011) · American Journal on Intellectual and Developmental Disabilities · doi:10.1352/1944-7558-116.6.457 · Cited by 35
Minocycline increases phosphorylation and membrane insertion of neuronal GluR1 receptors
Imbesi, M., Uz, T., Manev, R., Sharma, R. P., & Manev, H. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.10.006 · Cited by 34
Butyrate and acetyl‐carnitine inhibit the cytogenetic expression of the fragile X in vitro
Pomponi, M. G., & Neri, G. (1994) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320510428 · Cited by 26
Self-citationFryns, J. P., Kleczkowska, A., Kubień, E., & BERGHE, H. V. D. (1984) · Acta Paediatrica · doi:10.1111/j.1651-2227.1984.tb10001.x · Cited by 26
Cognition and lobar morphology in full mutation boys with fragile X syndrome
Meguid, N. A., Fahim, C., Sami, R., Nashaat, N. H., Yoon, U., Anwar, M., El-Dessouky, H. M., Shahine, E. A., Ibrahim, A. S., Mancini-Marı̈e, A., et al. (2011) · Brain and Cognition · doi:10.1016/j.bandc.2011.09.005 · Cited by 26
Silvestri, G., Rana, M., Odoardi, F., Modoni, A., Paris, E., Papacci, M., Tonali, P., & Servidei, S. (2000) · American Journal of Medical Genetics · doi:10.1002/1096-8628(20000918)94:3 · Cited by 25
Self-citationCommentary on population screening for fragile X syndrome
Coffee, B. W. (2010) · Genetics in Medicine · doi:10.1097/gim.0b013e3181e5c804 · Cited by 17
Intragenic probe used for diagnostics in fragile X families
Verkerk, A. J. M. H., De Vries, B. B. A., Niermeijer, M. F., Fu, Y., Nelson, D. L., Warren, S. T., Majoor‐Krakauer, D. F., Halley, D. J. J., & Oostra, B. A. (1992) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320430132 · Cited by 17
Godler, D. E., Slater, H. R., Amor, D. J., & Loesch, D. Z. (2010) · Genetics in Medicine · doi:10.1097/gim.0b013e3181f07088 · Cited by 11
Fragile X syndrome prenatal diagnosis: parental attitudes and reproductive responses
Xunclà, M., Badenas, C., Domínguez, M., Rodríguez-Revenga, L., Madrigal, I., Jiménez, L., Soler, A., Borrell, A., Sánchez, A., & Milà, M. (2010) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2010.05.015 · Cited by 9
[Informing members of families affected by fragile X syndrome of this diagnosis].
Carrasco, M. (2001) · PubMed · Cited by 2
Fragile X syndrome: is now the time for population screening?
Hantash, F. M. (2010) · PubMed · Cited by 2
La comunicación del diagnóstico a las familias afectadas por el síndrome X frágil
Mairena, M. C. (2001) · Revista de Neurología · doi:10.33588/rn.33s1.2001350 · Cited by 2
Classroom adaptations : Good practice and work habits
Braden, M. (2003) · doi:10.4324/9780203561539-16 · Cited by 1
Miller (1999) · doi:10.1002/(sici)1096-8628(19990402)83:4
Irwin (2001) · doi:10.1002/1096-8628(20010115)98:2
Flagged first, then by citations
Research works printed but not linked: 6
- Fryns, 1984, Acta Paediatr Scand Suppl., 313, 1
- Tassone F, et al. Newborn screening in fragile X syndrome: prevalence and allele distribution of the FMR1 gene. Paper presented at: American College of Medical Genetics Annual Clinical Genetics Meeting; July 26, 2012; Charlotte, North Carolina, USA. http://www.fragilex.org/community/international-fragile-x-conference/miami2012/agenda/ . Accessed October 19, 2012.
- Hantash, 2010, MLO Med Lab Obs., 42, 20
- Meguid, 2012, Brain Cogn., 78, 74
- Bakker, 1994, Cell., 78, 23
- Gatto, 2010, Front Synaptic Neurosci., 2, 4
Cited by
Sorted by citations
Autism spectrum disorder: neuropathology and animal models
Varghese, M., Keshav, N., Jacot-Descombes, S., Warda, T., Wicinski, B., Dickstein, D. L., Harony-Nicolas, H., De Rubeis, S., Drapeau, E., Buxbaum, J. D., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1736-4 · Cited by 536
Epidemiology of fragile X syndrome: A systematic review and meta‐analysis
Hunter, J. E., Rivero‐Arias, O., Angelov, A., Kim, E., Fotheringham, I., & Leal, J. (2014) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.36511 · Cited by 464
MMP ‐9 in translation: from molecule to brain physiology, pathology, and therapy
Vafadari, B., Salamian, A., & Kaczmarek, L. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13415 · Cited by 393
Translational control in synaptic plasticity and cognitive dysfunction
Buffington, S. A., Huang, W., & Costa-Mattioli, M. (2014) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071013-014100 · Cited by 348
A synaptic perspective of fragile X syndrome and autism spectrum Disorders.
Bagni, C., & Zukin, R. S. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.041 · Cited by 326
Self-citation
Metadata
- Authors
- Bagni, C., Tassone, F., Neri, G., & Hagerman, R.
- Affiliations
- KU Leuven (BE)
- University of California, Davis (US)
- Università Cattolica del Sacro Cuore (IT)
- Corresponding author
- Bagni, Claudia
- Venue
- Journal of Clinical Investigation
- Published
- 2012-12-03
- Volume
- 122
- Issue
- 12
- Pages
- 4314-4322
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3533539
- OpenAlex
- W2097267337
- Semantic Scholar
- d0bb26d811d90699694fe5287a4f71fdfc128aa8
- Cited by
- 321
- References
- 132
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 22 · 2023: 21 · 2022: 31 · 2021: 25 · 2020: 28 · 2019: 13 · 2018: 20 · 2017: 22 · 2016: 26 · 2015: 23 · 2014: 39 · 2013: 28
- FWCI
- 17.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion, other-oa)
- Lirias (submittedVersion, other-oa)
- Funders
- FRAXA Research Foundation
- Compagnia di San Paolo
- National Center for Research Resources (RR-024146, HD02274, HD036071, UL1RR024146)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD036071, HD 02274, P30HD002274, R01HD036071)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Keywords
- fragile X syndrome, FMR1 gene, FMRP, trinucleotide repeat expansion, intellectual disability, mRNA metabolism, receptor signaling, behavioral interventions, pharmacological interventions, cognitive intervention, autism spectrum disorder
- MeSH terms
- Animals, Autistic Disorder, Fragile X Syndrome, Humans, Synaptic Transmission, Early Diagnosis, Epigenesis, Genetic, Fragile X Messenger Ribonucleoprotein 1, Molecular Targeted Therapy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
