Cited by 634Genetics and Neurodevelopmental DisordersAutism Spectrum Disorder ResearchGenomic variations and chromosomal abnormalities

The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index; none of the 37 sources its claims cite is checked for support yet.

Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments

Open access

Leblond, Claire S., Nava, Caroline, Polge, Anne, Gauthier, Julie, Huguet, Guillaume, Lumbroso, Serge, Giuliano, Fabienne, Stordeur, Coline, Depienne, Christel, Mouzat, Kevin, Pinto, Dalila, Howe, Jennifer, Lemière, Nathalie, Durand, Christelle M., Guibert, Jessica, Ey, Elodie, Toro, Roberto, Peyre, Hugo, Mathieu, Alexandre, Amsellem, Frédérique, Rastam, Maria, Gillberg, I. Carina, Rappold, Gudrun A., Holt, Richard, Monaco, Anthony P., Maestrini, Elena, Galan, Pilar, Heron, Delphine, Jacquette, Aurélia, Afenjar, Alexandra, Rastetter, Agnès, Brice, Alexis, Devillard, Françoise, Assouline, Brigitte, Laffargue, Fanny, Lespinasse, James, Chiesa, Jean, Rivier, François, Bonneau, Dominique, Regnault, Beatrice, Zelenika, Diana, Delepine, Marc, Lathrop, Mark, Sanlaville, Damien, Schluth-Bolard, Caroline, Edery, Patrick, Perrin, Laurence, Tabet, Anne Claude, Schmeisser, Michael J., Boeckers, Tobias M., Coleman, Mary, Sato, Daisuke, Szatmari, Peter, Scherer, Stephen W., Rouleau, Guy A., Betancur, Catalina, Leboyer, Marion, Gillberg, Christopher, Delorme, Richard, Bourgeron, Thomas·2014·PLoS Genetics

DOI 10.1371/journal.pgen.1004580PMC PMC4154644

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Abstract

SHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice.

AI snapshot

Written from the paper’s full text.

TL;DR

This meta-analysis plus new screening found SHANK copy-number and truncating coding-sequence variants in ~1% of patients with ASD, with a gene-specific gradient of cognitive severity: SHANK1 in normal-IQ autism, SHANK2 in mild ID, and SHANK3 in moderate-to-profound ID. SHANK3 mutations were the most frequent and clinically relevant, accounting for more than 1 in 50 cases with ASD plus intellectual disability.

Key findings

SHANK1 mutations were rare: CNVs in 0.04% of ASD cases (2/5,657) versus 0/19,163 controls (meta-analysis fixed-effect P=0.19, OR=2.73, 95% CI 0.60–12.48), and no truncating coding-sequence variants were found (0/760 ASD, 0/492 controls). Damaging missense variants were more frequent in ASD (3.16% vs 1.02%, P=0.012, OR=3.17), but this did not survive Bonferroni correction; carriers had normal IQ (mean IQ=107) and ASD.
SHANK2 mutations were associated with mild ID: CNVs in 0.05% of ASD cases (3/5,657) versus 0/19,163 controls (P=0.076, OR=3.76), truncating coding-sequence variants in 0.12% (1/851 ASD vs 0/1,090 controls), and damaging missense variants in 4.58% vs 2.66% (P=0.025, OR=1.76). Carriers had mild to moderate ID (mean IQ=62±17).
SHANK3 mutations were most frequent and severe: CNVs in 0.18% of ASD cases (10/5,657) versus 0.01% of controls (2/19,163; P=0.019, OR=4.05), and truncating coding-sequence variants in 0.51% (11/2,147 ASD vs 0/1,031 controls; P=0.29, OR=2.85). In ASD with ID (IQ<70), de novo or truncating SHANK3 mutations reached 2.12% (CNVs 6/917=0.65%; coding-sequence 9/611=1.47%), versus 0% in ASD without ID and 0.01% in controls; carriers had moderate to severe/profound ID (mean IQ=31±8).
Across genes, truncating/CNV mutations were present in ~1% of ASD cases: SHANK1 0.04%, SHANK2 0.17%, SHANK3 0.69%, with a gradient from normal IQ (SHANK1) to mild ID (SHANK2) to moderate-to-profound ID (SHANK3).

Methods

Meta-analysis of SHANK copy-number variants (5,657 ASD cases and 19,163 controls from 11 studies, including this one) and coding-sequence variants (760–2,147 ASD cases and 492–1,090 controls depending on gene, from 10 studies, including this one). New screening included 46 ASD cases/454 controls for CNVs, 251 ASD cases/492 controls for SHANK1 exons, and 429 ASD cases/80 controls added to SHANK3 coding-sequence screening; de novo or truncating mutation carriers underwent extended clinical investigation.
ASD diagnosis used ADI-R, and in some cases ADOS or DISCO-10; IQ was measured with age-appropriate Wechsler scales, Raven’s Standard Progressive Matrices, or PPVT, plus systematic physical examination for dysmorphic and neurological features.
Statistical analysis used two-sided Fisher’s exact tests, Bonferroni correction for 12 tests (corrected α=0.0042), inverse-variance fixed- and random-effects meta-analysis, heterogeneity statistics (Q, I², Tau²), and power calculations; SHANK2 and SHANK3 reference sequences were corrected before screening.

Limitations

The paper states that inherited SHANK1 and SHANK2 variant associations did not survive Bonferroni correction, and the study was underpowered for low-effect-size inherited variants: power to detect an OR of 1.5 for SHANK1, SHANK2, and SHANK3 missense inherited damaging variants was 8%, 34%, and 17%, respectively; larger IQ-stratified cohorts are needed.
The paper notes that only non-synonymous mutations in known exons were screened; splicing isoforms, synonymous mutations, and regulatory variants were rarely reported, and whole-exome sequencing studies were excluded because of very low SHANK3 coverage. Some father DNA was unavailable for two SHANK3 truncating cases, two SHANK2 deletion patients were not included in prevalence calculations because the exact number screened was unavailable, and two unvalidated SHANK3 control deletions should be interpreted with caution.
Evident from the text: the meta-analysis relied on combining heterogeneous published cohorts, and although the authors contacted corresponding authors to avoid overlapping samples, control data for SHANK1 coding variants were incomplete in one prior study and were excluded from that analysis.

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Registry

Crossref · 10.1371/journal.pgen.1004580

Cites

58 of 58 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

0 of 37 cited sources checked · 0 supported · 0 flagged

A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we observed rare coding-sequence variants predicted as damaging in 4.58% of the patients with ASD compared with 2.66% of the controls (Fisher's exact test two-sided, P = 0.025, OR = 1.76, 95% CI = 1.05–2.97).”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > SHANK2 in ASD
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Rests on an assumption: Rare coding-sequence variants predicted as damaging by polyphen-2 are functionally deleterious.
A result the paper reports from its own data — 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 individuals carrying a SHANK2 de novo deletion were diagnosed with autistic disorder or pervasive developmental disorder not otherwise specified (PDD-NOS) in combination with mild to moderate ID (mean IQ = 62±17)”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > SHANK2 in ASD
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Rests on an assumption: Patients carrying de novo or truncating SHANK mutations who underwent clinical investigation are representative of all individuals with such mutations.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to prof”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Abstract
Load-bearingStrength:plain· not yet calibratedn = 5,657
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Rests on an assumption: The published studies included in the meta-analysis used comparable methods for detecting SHANK variants and comparable ASD/control ascertainment.
In the paper
“In the Canadian family, the elder sister carrying the SHANK3 duplication was diagnosed with attention-deficit/hyperactivity disorder (ADHD) and developmental delay [13].”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > SHANK3 in ASD
What the sources say
- Not checked yetcites [13] R Moessner, 2007, Contribution of SHANK3 mutations to autism spectrum disorder, Am J Hum Genet source
Strength:plain· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes

Show all 56 claims

Probably not a substantial claim. 26
It may state two separate claims as one. 26
The quote only partly states this claim. 2

A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“They also displayed minor signs of dysmorphism (broad nasal bridge, thin upper lip, pointed chin, clinodactyly) and abnormal neurological examination (Table 2).”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > SHANK2 in ASD
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: Patients carrying de novo or truncating SHANK mutations who underwent clinical investigation are representative of all individuals with such mutations.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“They displayed early signs of developmental delay, mild motor delay and significant language delay.”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > SHANK2 in ASD
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: Patients carrying de novo or truncating SHANK mutations who underwent clinical investigation are representative of all individuals with such mutations.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism”
- Also stated in: § SHANK1 in ASD · plain
  “deletions disrupting SHANK1 were detected in 0.04% (n = 2/5 657) of patients with ASD and were never found in 19 163 controls (Meta-analysis – Inverse variance method - fixed effect model P = 0.19, OR = 2.73, 95% CI = 0.60–12.48)”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Abstract
Load-bearingStrength:plain· not yet calibratedn = 2
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In three families from France and Canada, the SHANK3 deletions originated from a balanced translocation present in a healthy parent [6], [13].”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > SHANK3 in ASD
What the sources say
- Not checked yetcites [6] CM Durand, 2007, Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders, Nat Genet source
- Not checked yetcites [13] R Moessner, 2007, Contribution of SHANK3 mutations to autism spectrum disorder, Am J Hum Genet source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedn = 3
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably 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
“Interestingly, in two families, a sibling carried the reciprocal SHANK3 duplication.”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > SHANK3 in ASD
What the sources say
- Not checked yetcites [6] CM Durand, 2007, Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders, Nat Genet source
- Not checked yetcites [13] R Moessner, 2007, Contribution of SHANK3 mutations to autism spectrum disorder, Am J Hum Genet source
Strength:plain· not yet calibratedn = 2
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mutations of the SHANK genes were detected in the whole spectrum of ASD with a gradient of severity in cognitive impairment.”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Discussion
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The cohorts included in the meta-analysis are representative of the whole ASD population.
In the paper
“Interestingly, sex differences might modulate the phenotype since females carrying an inherited SHANK1 deletion exhibited anxiety and shyness, but did not fulfill criteria for ASD [19].”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > SHANK1 in ASD
What the sources say
- Not checked yetcites [19] D Sato, 2012, SHANK1 Deletions in Males with Autism Spectrum Disorder, Am J Hum Genet source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It 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
“In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment.”
- Also stated in: § Cohorts used for the meta-analysis of SHANK mutations · plain
  “Mutations in SHANK1-3 are associated with a gradient of severity in cognitive impairment.”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Abstract
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibratedn = 5,657
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The clinical phenotype associated with SHANK mutations is primarily attributable to the SHANK gene affected rather than to other genetic or environmental factors.
In the paper
“Here, we focused on the three SHANK genes, which code for large synaptic scaffold proteins of the post-synaptic density [12].”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Introduction
What the sources say
- Not checked yetcites [12] AM Grabrucker, 2011, Postsynaptic ProSAP/Shank scaffolds in the cross-hair of synaptopathies, Trends Cell Biol source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“male individuals carrying SHANK1 deletions do not present with language delay or ID and are diagnosed with normal IQ ASD or Asperger syndrome [19].”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Discussion
What the sources say
- Not checked yetcites [19] D Sato, 2012, SHANK1 Deletions in Males with Autism Spectrum Disorder, Am J Hum Genet source
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Previous functional studies have shown that inherited variants are associated with a statistically significant reduction in the density of synapses, although not as severe as the reduction caused by the de novo or truncating mutations [6], [18], [42]–[44].”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Discussion
What the sources say
- Not checked yetcites [6] CM Durand, 2007, Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders, Nat Genet source
- Not checked yetcites [18] CS Leblond, 2012, Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders, PLoS Genet source
- Not checked yetcites [42]–[44]
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“The two SHANK3 deletions reported by Glessner et al. (2009) [34] in control subjects have not been validated and should be interpreted with caution.”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > Cohorts used for the meta-analysis of SHANK mutations
What the sources say
- Not checked yetcites [34] JT Glessner, 2009, Autism genome-wide copy number variation reveals ubiquitin and neuronal genes, Nature source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It 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
“In summary, our genetic and clinical findings provide additional support for considering SHANK mutations in a broad spectrum of patients with ASD.”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Discussion
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passes
Probably not a substantial claim. It may be too vague to check against evidence.
- Rests on an assumption: The cohorts included in the meta-analysis are representative of the whole ASD population.
In the paper
“It has been proposed that abnormal SHANK levels at the synapse might result in the mislocalization, de-clustering and/or functional impairment of several other crucial synaptic proteins such as cytoskeletal regulators and/or neurotransmitter receptors [12] (Table 3).”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Discussion
What the sources say
- Not checked yetcites [12] AM Grabrucker, 2011, Postsynaptic ProSAP/Shank scaffolds in the cross-hair of synaptopathies, Trends Cell Biol source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“For SHANK1, there are two studies (Sato et al. (2012) [19] and this study), but Sato et al. (2012) [19] did not screen for all SHANK1 exons in the controls. Therefore these controls were not included here.”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > Cohorts used for the meta-analysis of SHANK mutations
What the sources say
- Not checked yetcites [19] D Sato, 2012, SHANK1 Deletions in Males with Autism Spectrum Disorder, Am J Hum Genet source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“other genes involved in the same synaptic pathway, including neurexin and neuroligin genes, appear to be associated with a variety of neuropsychiatric disorders [11].”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Discussion
What the sources say
- Not checked yetcites [11] TC Sudhof, 2008, Neuroligins and neurexins link synaptic function to cognitive disease, Nature source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“For controls, the two SHANK3 deletions reported by Glessner et al. (2009) among 2 519 individuals, were not validated and thus should be regarded with caution.”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Materials and Methods > SHANK copy-number and coding-sequence variants in ASD
What the sources say
- Not checked yetcites Glessner et al. (2009) source
Strength:plain· not yet calibratedn = 2,519
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.

53 of 53

The paper relies on this without support.
The published studies included in the meta-analysis used comparable methods for detecting SHANK variants and comparable ASD/control ascertainment.
“This meta-analysis included the published data from 14 studies in addition to a new screening of SHANK copy-number variants and coding sequence variants.”
The paper relies on this without support.
Rare coding-sequence variants predicted as damaging by polyphen-2 are functionally deleterious.
“rare inherited coding-sequence variants predicted as damaging were, however, more frequent in patients with ASD than in controls”
The paper relies on this without support.
The clinical phenotype associated with SHANK mutations is primarily attributable to the SHANK gene affected rather than to other genetic or environmental factors.
“Mutations in SHANK1-3 are associated with a gradient of severity in cognitive impairment.”
The paper relies on this without support.
Patients carrying de novo or truncating SHANK mutations who underwent clinical investigation are representative of all individuals with such mutations.
“When possible, the patients carrying truncating mutations altering SHANK genes underwent further clinical investigations (Table 2 & S7).”
The paper relies on this without support.
The cohorts included in the meta-analysis are representative of the whole ASD population.
“In the whole spectrum of ASD, we estimated that 0.04%, 0.17% and 0.69% of cases with ASD had heterozygous truncating mutations in SHANK1, SHANK2 or SHANK3, respectively (Table 1).”
The paper relies on this without support.
The control groups included in the meta-analysis are representative of the general population without ASD.
“0.01% in controls”
The paper relies on this without support.
The SHANK mutations classified as truncating or damaging are pathogenic.
“we estimated that 0.04%, 0.17% and 0.69% of cases with ASD had heterozygous truncating mutations in SHANK1, SHANK2 or SHANK3, respectively (Table 1).”

7 of 7

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?

Measuring inconsistency in meta-analyses
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003) · BMJ · doi:10.1136/bmj.327.7414.557 · Cited by 63,139 · cited 1×
“The Q statistic is a chisquare test for heterogeneity, and the I(2) and Tau(2) are the proportion of observed variance in effect sizes across studies for fixed effect model and random effect model, respectively [55].”
Method
Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders
Lord, C., Rutter, M., & Le Couteur, A. (1994) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02172145 · Cited by 9,065 · cited 4×
“In Sweden, in few cases, the Diagnostic Interview for Social and Communication Disorders (DISCO-10) [50] was used instead of the ADI-R.”
MethodInfluential
The Autism Diagnostic Observation Schedule—Generic: A Standard Measure of Social and Communication Deficits Associated with the Spectrum of Autism
Lord, C., Risi, S., Lambrecht, L., Cook, E. H., Leventhal, B. L., DiLavore, P. C., Pickles, A., & Rutter, M. (2000) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1005592401947 · Cited by 7,520 · cited 1×
“The autism-spectrum diagnosis was based on the Autism Diagnostic Interview – Revised (ADI-R) [48] and for some of the patients, the Autism Diagnostic Observation Schedule (ADOS) [49].”
Method
THE USE OF CONFIDENCE OR FIDUCIAL LIMITS ILLUSTRATED IN THE CASE OF THE BINOMIAL
Clopper, C. J., & Pearson, E. S. (1934) · Biometrika · doi:10.1093/biomet/26.4.404 · Cited by 5,327 · cited 1×
“Prevalence and confidence intervals of single studies were evaluated using Clopper and Pearson method [54].”
Method
Strong association of de novo copy number mutations with autism
Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J., et al. (2007) · Science · doi:10.1126/science.1138659 · Cited by 2,795 · cited 1×
“For the second patient AUN_007, the deletion covers the exon 22 of SHANK3 and exons 1 to 3 of ACR .”
Background
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
O’Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., et al. (2012) · Nature · doi:10.1038/nature10989 · Cited by 2,165 · cited 1×
“[32,36,37] and no truncating coding-sequence variation within SHANK1 and SHANK3.”
Background
De novo mutations revealed by whole-exome sequencing are strongly associated with autism
Sanders, S. J., Murtha, M. T., Gupta, A. R., Murdoch, J. D., Raubeson, M. J., Willsey, A. J., Ercan-Sencicek, A. G., DiLullo, N. M., Parikshak, N. N., Stein, J. L., et al. (2012) · Nature · doi:10.1038/nature10945 · Cited by 2,084 · cited 2×
“[32,36,37] and no truncating coding-sequence variation within SHANK1 and SHANK3.”
BackgroundResult
Functional impact of global rare copy number variation in autism spectrum disorders
Pinto, D., Pagnamenta, A. T., Klei, L., Anney, R., Merico, D., Regan, R., Conroy, J., Magalhaes, T. R., Correia, C., Abrahams, B. S., et al. (2010) · Nature · doi:10.1038/nature09146 · Cited by 2,013 · cited 2×
“SHANK copy-number and coding-sequence variants in ASD SHANK copy-number variants were detected with the Illumina Human 1M-Duo BeadChip, and validated by quantitative PCR as previously described [8,18].”
MethodSelf-citation
Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism
Study, P. A. R. I. S., Jamain, S., Quach, H., Betancur, C., Råstam, M., Colineaux, C., Gillberg, I. C., Soderstrom, H., Giros, B., Leboyer, M., et al. (2003) · Nature Genetics · doi:10.1038/ng1136 · Cited by 1,851 · cited 1×
“In particular, mutations in genes coding for synaptic cell adhesion molecules and scaffold proteins — such as neuroligins, neurexins and SHANK — have been repeatedly reported in individuals with ASD [5–10].”
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Neuroligins and neurexins link synaptic function to cognitive disease
Südhof, T. C. (2008) · Nature · doi:10.1038/nature07456 · Cited by 1,849 · cited 2×
“These proteins play a crucial role in the formation and stabilization of synapses [11,12].”
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Autism-associated SHANK3 missense point mutations impact conformational fluctuations and protein turnover at synapses
Bucher, M., Niebling, S., Han, Y., Molodenskiy, D., Hassani Nia, F., Kreienkamp, H.-J., Svergun, D., Kim, E., Kostyukova, A. S., Kreutz, M. R., et al. (2021) · eLife · doi:10.7554/elife.66165 · Cited by 33
Characterization of the Statistical Signatures of Micro-Movements Underlying Natural Gait Patterns in Children with Phelan McDermid Syndrome: Towards Precision-Phenotyping of Behavior in ASD
Torres, E. B., Nguyen, J., Mistry, S., Whyatt, C. P., Kalampratsidou, V., & Kolevzon, A. (2016) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2016.00022 · Cited by 31
Deficits in the Proline-Rich Synapse-Associated Shank3 Protein in Multiple Neuropsychiatric Disorders
Alexandrov, P. N., Zhao, Y., Jaber, V. R., Cong, L., & Lukiw, W. J. (2017) · Frontiers in Neurology · doi:10.3389/fneur.2017.00670 · Cited by 31
Dosage-sensitive genes in autism spectrum disorders: From neurobiology to therapy
Javed, S., Selliah, T., Lee, Y., & Huang, W. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.08.009 · Cited by 32
Biomedical knowledge graph embeddings for personalized medicine: Predicting disease‐gene associations
Vilela, J. E. R., Asif, M., Marques, A. R., Santos, J. X., Rasga, C., Vicente, A. M., & Martiniano, H. (2022) · Expert Systems · doi:10.1111/exsy.13181 · Cited by 36
Plasticity of postsynaptic nanostructure
Droogers, W. J., & MacGillavry, H. D. (2023) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2023.103819 · Cited by 28
Modeling SHANK3-associated autism spectrum disorder in Beagle dogs via CRISPR/Cas9 gene editing
Tian, R., Li, Y., Zhao, H., Lyu, W., Zhao, J., Wang, X., Lu, H., Xu, H., Ren, W., Tan, Q.-Q., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02276-9 · Cited by 31
Modulation of the Genome and Epigenome of Individuals Susceptible to Autism by Environmental Risk Factors
Koufaris, C., & Sismani, C. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16048699 · Cited by 35
Implication de l’épigénétique dans les troubles du spectre autistique : revue de la littérature
Hamza, M., Halayem, S., M’rad, R., Bourgou, S., Charfi, F., & Belhadj, A. (2016) · L Encéphale · doi:10.1016/j.encep.2016.07.007 · Cited by 38
Integrated transcriptome analysis of human iPS cells derived from a fragile X syndrome patient during neuronal differentiation
Lü, P., Chen, X., Feng, Y., Zeng, Q., Jiang, C., Zhu, X., Fan, G., & Xue, Z. (2016) · Science China Life Sciences · doi:10.1007/s11427-016-0194-6 · Cited by 32
Subacute Neuropsychiatric Syndrome in Girls WithSHANK3Mutations Responds to Immunomodulation
Bey, A. L., Gorman, M., Gallentine, W. B., Kohlenberg, T. M., Frankovich, J., Jiang, Y., & van Haren, K. P. (2020) · PEDIATRICS · doi:10.1542/peds.2019-1490 · Cited by 28
Nuclear receptor corepressors in intellectual disability and autism
Kong, Y., Zhou, W., & Sun, Z. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0667-y · Cited by 29
Sensory Reactivity Phenotype in Phelan–McDermid Syndrome Is Distinct from Idiopathic ASD
Tavassoli, T., Layton, C., Levy, T., Rowe, M. A., George-Jones, J., Zweifach, J., Lurie, S., Buxbaum, J. D., Kolevzon, A., & Siper, P. M. (2021) · Genes · doi:10.3390/genes12070977 · Cited by 33
Inhibitory dysfunction and social processing difficulties in autism: A comprehensive narrative review
Parrella, N.-F., Hill, A. T., Dipnall, L. M., Loke, Y. J., Enticott, P. G., & Ford, T. C. (2023) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2023.11.014 · Cited by 33
Dissecting the Genetics of Autism Spectrum Disorders: A Drosophila Perspective
Bellosta, P., & Soldano, A. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00987 · Cited by 32
A systematic review of common genetic variation and biological pathways in autism spectrum disorder
Rodríguez-Gomez, D. A., García-Guáqueta, D. P., Charry-Sánchez, J. D., Sarquis-Buitrago, E., Blanco, M., Vélez-van-Meerbeke, A., & Talero‐Gutiérrez, C. (2021) · BMC Neuroscience · doi:10.1186/s12868-021-00662-z · Cited by 36
Meta-analysis of epigenome-wide association studies of major depressive disorder
Li, Q. S., Morrison, R. L., Turecki, G., & Drevets, W. C. (2022) · Scientific Reports · doi:10.1038/s41598-022-22744-6 · Cited by 37
Excessive self-grooming, gene dysregulation and imbalance between the striosome and matrix compartments in the striatum of Shank3 mutant mice
Ferhat, A.-T. L. S., Verpy, E., Biton, A., Forget, B., de Chaumont, F., Mueller, F., Sourd, A. L., Coqueran, S., Schmitt, J., Rochefort, C., et al. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1139118 · Cited by 27
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Neurobiology and treatment of social cognition in schizophrenia: Bridging the bed-bench gap
Kimoto, S., Makinodan, M., & Kishimoto, T. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.10.022 · Cited by 33
Rare genetic brain disorders with overlapping neurological and psychiatric phenotypes
Peall, K. J., Owen, M. J., & Hall, J. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00896-x · Cited by 33
Sipa1l3/SPAR3 is targeted to postsynaptic specializations and interacts with the Fezzin ProSAPiP1/Lzts3
Dolnik, A., Kanwal, N., Mackert, S., Halbedl, S., Proepper, C., Bockmann, J., Schoen, M., Boeckers, T. M., Kühl, S. J., & Schmeißer, M. J. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13353 · Cited by 29
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Autism‐associated Shank3 mutations alter mGluR expression and mGluR‐dependent but not NMDA receptor‐dependent long‐term depression
Lee, K., Vyas, Y., Garner, C. C., & Montgomery, J. M. (2019) · Synapse · doi:10.1002/syn.22097 · Cited by 28
Inhibitory regulation of calcium transients in prefrontal dendritic spines is compromised by a nonsense Shank3 mutation
Ali, F., Shao, L.-X., Gerhard, D. M., Sweasy, K., Pothula, S., Pittenger, C., Duman, R. S., & Kwan, A. C. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0708-6 · Cited by 25
Molecular architecture of postsynaptic Interactomes
Wilkinson, B., & Coba, M. P. (2020) · Cellular Signalling · doi:10.1016/j.cellsig.2020.109782 · Cited by 25
Genetic Overlap Between Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in SHANK2 Gene
Ma, S. L., Chen, L. H., Lee, C., Lai, K. Y. C., Hung, S., Tang, C.-P., Ho, T., Shea, C. K., Mo, F. Y. M., Mak, T. S. H., et al. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.649588 · Cited by 29
DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study
Fuemmeler, B. F., Dozmorov, M. G., Do, E. K., Zhang, J. J., Grenier, C., Huang, Z., Maguire, R. L., Kollins, S. H., Hoyo, C., & Murphy, S. K. (2021) · Environmental Health Perspectives · doi:10.1289/ehp8099 · Cited by 30
Prenatal Zinc Deficient Mice as a Model for Autism Spectrum Disorders
Sauer, A. K., Hagmeyer, S., & Grabrucker, A. M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116082 · Cited by 35
11q24.2‐25 micro‐rearrangements in autism spectrum disorders: Relation to brain structures
Maruani, A., Huguet, G., Beggiato, A., Elmaleh, M., Toro, R., Leblond, C. S., Mathieu, A., Amsellem, F., Lemière, N., Verloès, A., et al. (2015) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.37345 · Cited by 30
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Enlarged dendritic spines and pronounced neophobia in mice lacking the PSD protein RICH2
Sarowar, T., Grabrucker, S., Föhr, K. J., Mangus, K., Eckert, M., Bockmann, J., Boeckers, T. M., & Grabrucker, A. M. (2016) · Molecular Brain · doi:10.1186/s13041-016-0206-6 · Cited by 32
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An altered glial phenotype in the NL3R451C mouse model of autism
Matta, S. M., Moore, Z., Walker, F. R., Hill‐Yardin, E. L., & Crack, P. J. (2020) · Scientific Reports · doi:10.1038/s41598-020-71171-y · Cited by 28
Shank3 Binds to and Stabilizes the Active Form of Rap1 and HRas GTPases via Its NTD-ANK Tandem with Distinct Mechanisms
Cai, Q., Hosokawa, T., Zeng, M., Hayashi, Y., & Zhang, M. (2019) · Structure · doi:10.1016/j.str.2019.11.018 · Cited by 26
Brain-Enriched Coding and Long Non-coding RNA Genes Are Overrepresented in Recurrent Neurodevelopmental Disorder CNVs
Alinejad‐Rokny, H., Heng, J. I., & Forrest, A. R. R. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108307 · Cited by 30
Long-Lasting Changes in Glial Cells Isolated From Rats Subjected to the Valproic Acid Model of Autism Spectrum Disorder
Traetta, M. E., Uccelli, N. A., Zárate, S., Cuautle, D. G., Ramos, A. J., & Reinés, A. G. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.707859 · Cited by 28
Shank3‐deficient rats exhibit degraded cortical responses to sound
Engineer, C. T., Rahebi, K. C., Borland, M. S., Buell, E. P., Im, K. W., Wilson, L. G., Sharma, P., Vanneste, S., Harony‐Nicolas, H., Buxbaum, J. D., et al. (2017) · Autism Research · doi:10.1002/aur.1883 · Cited by 26
Live Mouse Tracker: real-time behavioral analysis of groups of micePreprint
de Chaumont, F., Ey, E., Torquet, N., Lagache, T., Dallongeville, S., Imbert, A., Legou, T., Lesourd, A., Faure, P., Bourgeron, T., et al. (2018) · bioRxiv · doi:10.1101/345132 · Cited by 32
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Functional genomics analysis of Phelan-McDermid syndrome 22q13 region during human neurodevelopment
Ziats, C. A., Grosvenor, L. P., Sarasua, S. M., Thurm, A. E., Swedo, S. E., Mahfouz, A. E., Rennert, O. M., & Ziats, M. N. (2019) · PLoS ONE · doi:10.1371/journal.pone.0213921 · Cited by 25
Activation of the medial preoptic area (MPOA) ameliorates loss of maternal behavior in a Shank2 mouse model for autism
Grabrucker, S., Pagano, J., Schweizer, J., Urrutia‐Ruiz, C., Schön, M., Thome, K., Ehret, G., Grabrucker, A. M., Zhang, R., Hengerer, B., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2019104267 · Cited by 28
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Language ENvironment Analysis (LENA) in Phelan-McDermid Syndrome: Validity and Suggestions for Use in Minimally Verbal Children with Autism Spectrum Disorder
Rankine, J., Li, E., Lurie, S., Rieger, H., Fourie, E., Siper, P. M., Wang, A. T., Buxbaum, J. D., & Kolevzon, A. (2017) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-017-3082-8 · Cited by 25
Genetics implicate common mechanisms in autism and schizophrenia: synaptic activity and immunity
Liu, X., Li, Z., Fan, C., Zhang, D., & Chen, J. (2017) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2016-104487 · Cited by 27
Coupling of autism genes to tissue-wide expression and dysfunction of synapse, calcium signalling and transcriptional regulation
Reilly, J., Gallagher, L., Leader, G., & Shen, S. (2020) · PLoS ONE · doi:10.1371/journal.pone.0242773 · Cited by 25
Zinc deficiency and supplementation in autism spectrum disorder and Phelan‐McDermid syndrome
Alsufiani, H. M., Alkhanbashi, A. S., Laswad, N. A. B., Bakhadher, K. K., AlGhamdi, S. A., Tayeb, H. O., & Tarazi, F. I. (2022) · Journal of Neuroscience Research · doi:10.1002/jnr.25019 · Cited by 28
From bench to bedside: The mGluR5 system in people with and without Autism Spectrum Disorder and animal model systems
Carey, C., Singh, N., Dunn, J., Sementa, T., Méndez, M. A., Velthuis, H., Pereira, A. C., Pretzsch, C. M., Horder, J., Hader, S., et al. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02143-1 · Cited by 33
Aberrant cognitive phenotypes and altered hippocampal BDNF expression related to epigenetic modifications in mice lacking the post‐synaptic scaffolding protein SHANK1: Implications for autism spectrum disorder
Sungur, A. Ö., Jochner, M. C. E., Harb, H., Kılıç, A., Garn, H., Schwarting, R. K. W., & Wöhr, M. (2017) · Hippocampus · doi:10.1002/hipo.22741 · Cited by 30
Structural basis for PDZ domain interactions in the post‐synaptic density scaffolding protein Shank3
Ponna, S. K., Ruskamo, S., Myllykoski, M., Keller, C., Boeckers, T. M., & Kursula, P. (2018) · Journal of Neurochemistry · doi:10.1111/jnc.14322 · Cited by 25
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Truncating mutations in SHANK3 associated with global developmental delay interfere with nuclear β‐catenin signaling
Nia, F. H., Woike, D., Kloth, K., Kortüm, F., & Kreienkamp, H. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15014 · Cited by 26
Integrative genomic analyses for identification and prioritization of long non-coding RNAs associated with autism
Gudenas, B. L., Srivastava, A. K., & Wang, L. (2017) · PLoS ONE · doi:10.1371/journal.pone.0178532 · Cited by 26
Gene constraint and genotype–phenotype correlations in neurodevelopmental disorders
Betancur, C., & Buxbaum, J. D. (2020) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.05.036 · Cited by 24
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A randomized controlled trial of intranasal oxytocin in Phelan-McDermid syndrome
Fastman, J., Foss‐Feig, J. H., Frank, Y., Halpern, D. B., Harony‐Nicolas, H., Layton, C., Sandin, S., Siper, P. M., Tang, L., Trelles, M. P., et al. (2021) · Molecular Autism · doi:10.1186/s13229-021-00459-1 · Cited by 27
Dietary zinc supplementation rescues fear-based learning and synaptic function in the Tbr1+/− mouse model of autism spectrum disorders
Lee, K., Jung, Y., Vyas, Y., Skelton, I., Abraham, W. C., Hsueh, Y., & Montgomery, J. M. (2022) · Molecular Autism · doi:10.1186/s13229-022-00494-6 · Cited by 24
Common Ribs of Inhibitory Synaptic Dysfunction in the Umbrella of Neurodevelopmental Disorders
Rodriguez, R. A., Joya, C., & Hines, R. M. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00132 · Cited by 25
Induced pluripotent stem cells as a tool to study brain circuits in autism-related disorders
Vitrac, A., & Cloëz-Tayarani, I. (2018) · Stem Cell Research & Therapy · doi:10.1186/s13287-018-0966-2 · Cited by 28
Shank2 Mutant Mice Display Hyperactivity Insensitive to Methylphenidate and Reduced Flexibility in Social Motivation, but Normal Social Recognition
Ey, E., Torquet, N., de Chaumont, F., Lévi‐Strauss, J., Ferhat, A.-T. L. S., Sourd, A. L., Boeckers, T. M., & Bourgeron, T. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00365 · Cited by 21
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Shank2 Binds to aPKC and Controls Tight Junction Formation with Rap1 Signaling during Establishment of Epithelial Cell Polarity
Sasaki, K., Kojitani, N., Hirose, H., Yoshihama, Y., Suzuki, H., Shimada, M., Takayanagi, A., Yamashita, A., Nakaya, M., Hirano, H., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.02.088 · Cited by 23
Severe white matter damage in SHANK3 deficiency: a human and translational study
Jesse, S., Müller, H., Schoen, M., Asoglu, H., Bockmann, J., Huppertz, H., Rasche, V., Ludolph, A. C., Boeckers, T. M., & Kassubek, J. (2019) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.50959 · Cited by 29
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Embryonic Arsenic Exposure Triggers Long-Term Behavioral Impairment with Metabolite Alterations in Zebrafish
Bakar, N. A., Ibrahim, W. N. W., Abdullah, C. A. C., Ramlan, N. F., Shaari, K., Shohaimi, S., Mediani, A., Nasruddin, N. S., Kim, C., & Faudzi, S. M. M. (2022) · Toxics · doi:10.3390/toxics10090493 · Cited by 25
Zinc Status and Autism Spectrum Disorder in Children and Adolescents: A Systematic Review
do Nascimento, P. K. D. S. B., Silva, D. F. O., de Morais, T. L. S. A., & de Rezende, A. A. (2023) · Nutrients · doi:10.3390/nu15163663 · Cited by 24
Shanks — multidomain molecular scaffolds of the postsynaptic density
Kursula, P. (2019) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2019.01.007 · Cited by 22
SHANK3 conformation regulates direct actin binding and crosstalk with Rap1 signaling
Salomaa, S. I., Miihkinen, M., Kremneva, E., Paatero, I., Lilja, J., Jacquemet, G., Vuorio, J., Antenucci, L., Kogan, K., Nia, F. H., et al. (2021) · Current Biology · doi:10.1016/j.cub.2021.09.022 · Cited by 27
A recurrent SHANK3 frameshift variant in Autism Spectrum Disorder
Loureiro, L. O., Howe, J., Reuter, M. S., Iaboni, A., Calli, K., Roshandel, D., Pritišanac, I., Moses, A. M., Forman-Kay, J. D., Trost, B., et al. (2021) · npj Genomic Medicine · doi:10.1038/s41525-021-00254-0 · Cited by 30
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Sleep disturbances in autism spectrum disorder: Animal models, neural mechanisms, and therapeutics
Maurer, J. J., Choi, A., An, I., Sathi, N., & Chung, S. (2023) · Neurobiology of Sleep and Circadian Rhythms · doi:10.1016/j.nbscr.2023.100095 · Cited by 31
Altered nocifensive behavior in animal models of autism spectrum disorder: The role of the nicotinic cholinergic system
Wang, L., Almeida, L. E. F., Nettleton, M. Y., Khaibullina, A., Albani, S. H., Kamimura, S., Nouraie, M. S., & Quezado, Z. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.09.013 · Cited by 25
Worms on the spectrum - C. elegans models in autism research
Schmeißer, K., & Parker, J. A. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.04.007 · Cited by 26
Bio-collections in autism research
Reilly, J., Gallagher, L., Chen, J. L., Leader, G., & Shen, S. (2017) · Molecular Autism · doi:10.1186/s13229-017-0154-8 · Cited by 23
Behavioral phenotypes and neurobiological mechanisms in the Shank1 mouse model for autism spectrum disorder: A translational perspective
Sungur, A. Ö., Schwarting, R. K. W., & Wöhr, M. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.09.038 · Cited by 24
Neural selectivity for communicative auditory signals in Phelan-McDermid syndrome
Wang, A. T., Lim, T., Jamison, J., Bush, L., Soorya, L. V., Tavassoli, T., Siper, P. M., Buxbaum, J. D., & Kolevzon, A. L. (2016) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-016-9138-9 · Cited by 23
Social Deficits and Repetitive Behaviors Are Improved by Early Postnatal Low-Dose VPA Intervention in a Novel shank3-Deficient Zebrafish Model
Liu, C., Wang, Y., Deng, J., Lin, J., Hu, C., Li, Q., & Xu, X. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.682054 · Cited by 25
Rare copy number variants are common in young children with autism spectrum disorder
Eriksson, M. A., Liedén, A., Westerlund, J., Bremer, A., Wincent, J., Sahlin, E., Gillberg, C., Fernell, E., & Anderlid, B. (2015) · Acta Paediatrica · doi:10.1111/apa.12969 · Cited by 25
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Association between SHANK3 polymorphisms and susceptibility to autism spectrum disorder
Qiu, S., Li, Y., Li, Y., Zhong, W., Shi, M., Zhao, Q., Zhang, K., Wang, Y., Lu, M., Zhu, X., et al. (2018) · Gene · doi:10.1016/j.gene.2018.01.078 · Cited by 23
Autism spectrum disorders: autistic phenotypes and complicated mechanisms
Zhang, X.-C., Shu, L., Zhao, X., & Li, X. (2019) · World Journal of Pediatrics · doi:10.1007/s12519-018-0210-2 · Cited by 22
Shank3 oligomerization governs material properties of the postsynaptic density condensate and synaptic plasticity
Jia, B., Shen, Z., Zhu, S., Huang, J., Liao, Z., Zhao, S., Li, H., Chen, S., Xu, Y., Wang, Y., et al. (2025) · Cell · doi:10.1016/j.cell.2025.07.047 · Cited by 25
Developmental convergence and divergence in human stem cell models of autism
Gordon, A., Yoon, S., Bicks, L. K., Martín, J. M., Pintacuda, G., Arteaga, S. A., Wamsley, B., Guo, Q., Elahi, L. S., Dolmetsch, R. E., et al. (2026) · Nature · doi:10.1038/s41586-025-10047-5 · Cited by 42
Age, brain region, and gene dosage-differential transcriptomic changes in Shank3-mutant mice
Yoo, T., Yoo, Y.-E., Kang, H., & Kim, E. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1017512 · Cited by 19
A critical role of spinal Shank2 proteins in NMDA-induced pain hypersensitivity
Yoon, S. Y., Kwon, S.-G., Kim, Y. H., Yeo, J., Ko, H., Roh, D., Kaang, B., Beitz, A. J., Lee, J., & Oh, S. B. (2017) · Molecular Pain · doi:10.1177/1744806916688902 · Cited by 21
Cognitive impairment and autistic-like behaviour in SAPAP4-deficient mice
Schob, C., Morellini, F., Ohana, O., Bakota, L., Hrynchak, M. V., Brandt, R., Brockmann, M. D., Cichon, N., Hartung, H., Hanganu‐Opatz, I. L., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-018-0327-z · Cited by 21
Shank2/3 double knockout-based screening of cortical subregions links the retrosplenial area to the loss of social memory in autism spectrum disorders
Garrido, D., Beretta, S., Grabrucker, S., Bauer, H. F., Bayer, D., Sala, C., Verpelli, C., Roselli, F., Bockmann, J., Proepper, C., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01756-8 · Cited by 26
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Tackling hypo and hyper sensory processing heterogeneity in autism: From clinical stratification to genetic pathways
Lefebvre, A., Tillmann, J., Cliquet, F., Amsellem, F., Maruani, A., Leblond, C. S., Beggiato, A., Germanaud, D., Amestoy, A., Moal, M. L., et al. (2022) · Autism Research · doi:10.1002/aur.2861 · Cited by 19
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Immune activation during pregnancy exacerbates ASD-related alterations in Shank3-deficient mice
Atanasova, E., Arévalo, A. P., Graf, I., Zhang, R., Bockmann, J., Lutz, A.-K., & Boeckers, T. M. (2023) · Molecular Autism · doi:10.1186/s13229-022-00532-3 · Cited by 21
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Dissecting the 22q13 region to explore the genetic and phenotypic diversity of patients with Phelan-McDermid syndrome
Vitrac, A., Leblond, C. S., Rolland, T., Cliquet, F., Mathieu, A., Maruani, A., Delorme, R., Schön, M., Grabrucker, A. M., van Ravenswaaij‐Arts, C. M. A., et al. (2023) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2023.104732 · Cited by 22
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Bridging the translational gap: what can synaptopathies tell us about autism?
Molloy, C. J., Cooke, J., Gatford, N. J. F., Rivera-Olvera, A., Avazzadeh, S., Homberg, J. R., Grandjean, J., Fernandes, C., Shen, S., Loth, E., et al. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1191323 · Cited by 23
Synaptopathology in autism spectrum disorders: Complex effects of synaptic genes on neural circuits
Wang, X., Kéry, R., & Xiong, Q. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.09.026 · Cited by 24
Mouse models as a tool for discovering new neurological diseases
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Authors: Leblond, C. S., Nava, C., Polge, A., Gauthier, J., Huguet, G., Lumbroso, S., Giuliano, F., Stordeur, C., Depienne, C., Mouzat, K., Pinto, D., Howe, J., Lemière, N., Durand, C. M., Guibert, J., Ey, E., Toro, R., Peyre, H., Mathieu, A., Amsellem, F., Rastam, M., Gillberg, I. C., Rappold, G. A., Holt, R., Monaco, A. P., Maestrini, E., Galan, P., Heron, D., Jacquette, A., Afenjar, A., Rastetter, A., Brice, A., Devillard, F., Assouline, B., Laffargue, F., Lespinasse, J., Chiesa, J., Rivier, F., Bonneau, D., Regnault, B., Zelenika, D., Delepine, M., Lathrop, M., Sanlaville, D., Schluth-Bolard, C., Edery, P., Perrin, L., Tabet, A. C., Schmeisser, M. J., Boeckers, T. M., Coleman, M., Sato, D., Szatmari, P., Scherer, S. W., Rouleau, G. A., Betancur, C., Leboyer, M., Gillberg, C., Delorme, R., & Bourgeron, T.
Affiliations: Centre National de la Recherche Scientifique (FR)
Centre Hospitalier Universitaire de Nîmes (FR)
Centre Hospitalier Universitaire Sainte-Justine (CA)
Centre Hospitalier Universitaire de Nice (FR)
Icahn School of Medicine at Mount Sinai (US)
University of Toronto (CA)
Institut Pasteur (FR)
University of Gothenburg (SE)
Heidelberg University (DE)
Centre for Human Genetics (GB)
University of Bologna (IT)
Conservatoire National des Arts et Métiers (FR)
Assistance Publique – Hôpitaux de Paris (FR)
Hôpital Armand-Trousseau (FR)
Hôpital Couple Enfant (FR)
Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
Inserm (FR)
Lyon 1 Université (FR)
Universität Ulm (DE)
Montreal Neurological Institute and Hospital (CA)
University College London (GB)
Corresponding author: Bourgeron, Thomas
ORCID: Leblond, Claire S.
Nava, Caroline
Huguet, Guillaume
Lumbroso, Serge
Giuliano, Fabienne
Depienne, Christel
Pinto, Dalila
Durand, Christelle M.
Ey, Elodie
Toro, Roberto
Peyre, Hugo
Mathieu, Alexandre
Rappold, Gudrun A.
Monaco, Anthony P.
Maestrini, Elena
Galan, Pilar
Jacquette, Aurélia
Afenjar, Alexandra
Brice, Alexis
Laffargue, Fanny
Rivier, François
Bonneau, Dominique
Lathrop, Mark
Sanlaville, Damien
Edery, Patrick
Schmeisser, Michael J.
Boeckers, Tobias M.
Sato, Daisuke
Scherer, Stephen W.
Rouleau, Guy A.
Betancur, Catalina
Leboyer, Marion
Gillberg, Christopher
Delorme, Richard
Bourgeron, Thomas
Venue: PLoS Genetics
Publisher: Public Library of Science (PLoS)
Published: 2014-09-04
Volume: 10
Issue: 9
Pages: e1004580
ISSN: 1553-7390 (ISSN-L)
1553-7404
DOI: 10.1371/journal.pgen.1004580
PMC: PMC4154644
OpenAlex: W2141041915
Semantic Scholar: 765f93019a616c818b4b4525f202bb4aeb20152c
Cited by: 630
References: 58
Citations by year: 2026: 30 · 2025: 38 · 2024: 72 · 2023: 61 · 2022: 65 · 2021: 62 · 2020: 51 · 2019: 50 · 2018: 58 · 2017: 57 · 2016: 43 · 2015: 39 · 2014: 4
FWCI: 6.30
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS Genetics (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
HAL (submittedVersion, other-oa)
RePEc: Research Papers in Economics (submittedVersion)
Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
eScholarship@McGill (McGill) (submittedVersion)
Figshare (submittedVersion, cc-by)
Lund University Publications (Lund University) (submittedVersion, other-oa)
Funders: Fondation FondaMental
Fondation Cognacq-Jay
Fondation Orange
Deutsche Forschungsgemeinschaft
Agence Nationale de la Recherche (ANR-08-MNPS-0037)
Institut National de la Santé et de la Recherche Médicale
Centre National de la Recherche Scientifique
Université Paris Diderot
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords: autism spectrum disorder, SHANK3, Shank2, Shank1, copy number variation, truncating mutations, intellectual disability, cognitive impairment severity, de novo mutations, postsynaptic density, glutamatergic synapses, dendritic spines, mutation detection
MeSH terms: Child, Child Development Disorders, Pervasive, Cognition, Cognition Disorders, Female, Humans, Male, Intellectual Disability, Mutation, Nerve Tissue Proteins, Neurons, Synapses, Case-Control Studies, DNA Copy Number Variations

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Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments

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