Cited by 420Genetics and Neurodevelopmental DisordersGenetic Neurodegenerative DiseasesNeuroscience and Neuropharmacology Research

The DOI matches its Crossref record; 133 of the 133 references it cites were found in a registry or an index.

The Pathophysiology of Fragile X Syndrome

Penagarikano, Olga, Mulle, Jennifer G., Warren, Stephen T.·2007·Annual Review of Genomics and Human Genetics

DOI 10.1146/annurev.genom.8.080706.092249

Open this paper in CoChat — free account

Abstract

Fragile X syndrome is the most common form of inherited mental retardation. The disorder is mainly caused by the expansion of the trinucleotide sequence CGG located in the 5' UTR of the FMR1 gene on the X chromosome. The abnormal expansion of this triplet leads to hypermethylation and consequent silencing of the FMR1 gene. Thus, the absence of the encoded protein (FMRP) is the basis for the phenotype. FMRP is a selective RNA-binding protein that associates with polyribosomes and acts as a negative regulator of translation. FMRP appears to play an important role in synaptic plasticity by regulating the synthesis of proteins encoded by certain mRNAs localized in the dendrite. An advancing understanding of the pathophysiology of this disorder has led to promising strategies for pharmacologic interventions.

Integrity signals

Registry

Crossref · 10.1146/annurev.genom.8.080706.092249

Cites

133 of 133 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Initial sequencing and analysis of the human genome
International Human Genome Sequencing Consortium, Whitehead Institute for Biomedical Research, C. F. G. R., Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., Devon, K., Dewar, K., et al. (2001) · Nature · doi:10.1038/35057062 · Cited by 24,216
Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome
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
Self-citation
Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox
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
Self-citation
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
Self-citation
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
Self-citation
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
Self-citation
Structure and function of dendritic spines
Nimchinsky, E. A., Sabatini, B. L., & Svoboda, K. (2002) · Annual Review of Physiology · doi:10.1146/annurev.physiol.64.081501.160008 · Cited by 1,208
Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome
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
Self-citation
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
Role for rapid dendritic protein synthesis in hippocampal mGluR-dependent long-term depression.
Huber, K., Kayser, M., & Bear, M. (2000) · Science · doi:10.1126/science.288.5469.1254 · Cited by 1,015
Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function
Darnell, J. C., Jensen, K. B., Jin, P., Brown, V., Warren, S. T., & Darnell, R. B. (2001) · Cell · doi:10.1016/s0092-8674(01)00566-9 · Cited by 952
Self-citation
Repeat instability: mechanisms of dynamic mutations
Pearson, C. E., Edamura, K. N., & Cleary, J. D. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1689 · Cited by 924 · cited 1×
“Flaps containing repeats could acquire different DNA conformations that enable them to escape FEN-1 cleavage occur; massive expansions could take place by some continuous slippage due to a block in the replication process generated by alternative structures formed by the trinucleotide repeat sequences (89).”
Background
The FMR–1 protein is cytoplasmic, most abundant in neurons and appears normal in carriers of a fragile X premutation
Devys, D., Lutz, Y., Rouyer, N., Bellocq, J., & Mandel, J. (1993) · Nature Genetics · doi:10.1038/ng0893-335 · Cited by 781
FMR1 Protein: Conserved RNP Family Domains and Selective RNA Binding
Ashley, C. T., Wilkinson, K. D., Reines, D., & Warren, S. T. (1993) · Science · doi:10.1126/science.7692601 · Cited by 752
Self-citation
Protein synthesis at synaptic sites on dendrites.
Steward, O., & Schuman, E. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.299 · Cited by 731
Repeat instability : mechanisms of dynamic mutations
Pearson, C. E. (2005) · Medical Entomology and Zoology · Cited by 711
The Fragile X Syndrome Protein FMRP Associates with BC1 RNA and Regulates the Translation of Specific mRNAs at Synapses
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
Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation
Weiler, I. J., Irwin, S. A., Klintsova, A. Y., Spencer, C. M., Brazelton, A. D., Miyashiro, K., Comery, T. A., Patel, B., Eberwine, J., & Greenough, W. T. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.10.5395 · Cited by 644
Direct Diagnosis by DNA Analysis of the Fragile X Syndrome of Mental Retardation
Rousseau, F., Heitz, D., Biancalana, V., Blumenfeld, S., Kretz, C., Boué, J., Tommerup, N., Hagen, C. V. D., DeLozier-Blanchet, C. D., Croquette, M., et al. (1991) · New England Journal of Medicine · doi:10.1056/nejm199112123252401 · Cited by 643
The protein product of the fragile X gene, FMR1, has characteristics of an RNA-binding protein.
Siomi, H., Siomi, M. C., Nussbaum, R. L., & Dreyfuss, G. (1993) · Cell · doi:10.1016/0092-8674(93)90420-u · Cited by 641
A point mutation in the FMR-1 gene associated with fragile X mental retardation
Boulle, K. D., Verkerk, A. J. M. H., Reyniers, E., Vits, L., Hendrickx, J., Roy, B. V., Bos, F. V. D., de Graaff, E., Oostra, B. A., & Willems, P. J. (1993) · Nature Genetics · doi:10.1038/ng0193-31 · Cited by 624
A marker X chromosome.
Lubs, H. A. (1969) · PubMed · Cited by 610
Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway
Jin, P., Zarnescu, D. C., Ceman, S., Nakamoto, M., Mowrey, J., Jongens, T. A., Nelson, D. L., Moses, K., & Warren, S. T. (2004) · Nature Neuroscience · doi:10.1038/nn1174 · Cited by 604
Self-citation
Neuronal intranuclear inclusions in a new cerebellar tremor/ataxia syndrome among fragile X carriers
Greco, C. (2002) · Brain · doi:10.1093/brain/awf184 · Cited by 560
Abnormal Development of Dendritic Spines in FMR1 Knock-Out Mice
Nimchinsky, E. A., Oberlander, A. M., & Svoboda, K. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-14-05139.2001 · Cited by 560
Neuronal RNA Granules
Krichevsky, A. M., & Kosik, K. S. (2001) · Neuron · doi:10.1016/s0896-6273(01)00508-6 · Cited by 536
Fragile X mental retardation protein: Nucleocytoplasmic shuttling and association with somatodendritic ribosomes.
Feng, Y., Gutekunst, C.-A., Eberhart, D. E., Yi, H., Warren, S. T., & Hersch, S. M. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-05-01539.1997 · Cited by 532
Self-citation
Fragile Sites on Human Chromosomes: Demonstration of Their Dependence on the Type of Tissue Culture Medium
Sutherland, G. R. (1977) · Science · doi:10.1126/science.877551 · Cited by 528
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
Further segregation analysis of the fragile X syndrome with special reference to transmitting males
Sherman, S. L., Jacobs, P. A., Morton, N. E., Froster‐Iskenius, U., Howard‐Peebles, P. N., Nielsen, K. B., Partington, M. W., Sutherland, G. R., TURNER, G. M., & Watson, M. (1985) · Human Genetics · doi:10.1007/bf00291644 · Cited by 510
Association of FMR1 repeat size with ovarian dysfunction
Sullivan, A. K., Marcus, M., Epstein, M. P., Allen, E. G., Anido, A., Paquin, J. J., Yadav-Shah, M., & Sherman, S. L. (2004) · Human Reproduction · doi:10.1093/humrep/deh635 · Cited by 505
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
Pharmacological Rescue of Synaptic Plasticity, Courtship Behavior, and Mushroom Body Defects in a Drosophila Model of Fragile X Syndrome
McBride, S. M. J., Choi, C. H., Wang, Y., Liebelt, D. A., Braunstein, E. M., Ferreiro, D., Sehgal, A., Siwicki, K. K., Dockendorff, T. C., Nguyen, H. T., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.01.038 · Cited by 484
Length of uninterrupted CGG repeats determines instability in the FMR1 gene
Eichler, E. E., Holden, J. J. A., Popovich, B. W., Reiss, A. L., Snow, K., Thibodeau, S. N., Richards, C. S., Ward, P. A., & Nelson, D. L. (1994) · Nature Genetics · doi:10.1038/ng0994-88 · Cited by 481
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
Dynamic Translational and Proteasomal Regulation of Fragile X Mental Retardation Protein Controls mGluR-Dependent Long-Term Depression
Hou, L., Antion, M. D., Hu, D., Spencer, C. M., Paylor, R., & Klann, E. (2006) · Neuron · doi:10.1016/j.neuron.2006.07.005 · Cited by 469
Synaptic Protein Synthesis Associated with Memory Is Regulated by the RISC Pathway in Drosophila
Ashraf, S. I., McLoon, A. L., Sclarsic, S. M., & Kunes, S. M. (2006) · Cell · doi:10.1016/j.cell.2005.12.017 · Cited by 446
Drosophila as a Model for Human Neurodegenerative Disease
Bilen, J., & Bonini, N. M. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095804 · Cited by 431
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
Deletion of FMR1 in Purkinje Cells Enhances Parallel Fiber LTD, Enlarges Spines, and Attenuates Cerebellar Eyelid Conditioning in Fragile X Syndrome
Koekkoek, S. K. E., Yamaguchi, K., Milojkovic, B. A., Dortland, B. R., Ruigrok, T. J. H., Maex, R., Graaf, W. D., Smit, A. E., VanderWerf, F., Bakker, C. E., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.07.005 · Cited by 412
Metabotropic Glutamate Receptor Activation Regulates Fragile X Mental Retardation Protein and Fmr1 mRNA Localization Differentially in Dendrites and at Synapses
Antar, L. N., Afroz, R., Dictenberg, J. B., Carroll, R. C., & Bassell, G. J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0099-04.2004 · Cited by 411
The marker (X) syndrome: a cytogenetic and genetic analysis
Sherman, S. L., Morton, N. E., Jacobs, P. A., & TURNER, G. M. (1984) · Annals of Human Genetics · doi:10.1111/j.1469-1809.1984.tb00830.x · Cited by 386
NONCODING RNAS IN THE MAMMALIAN CENTRAL NERVOUS SYSTEM
Cao, X., Yeo, G., Muotri, A. R., Kuwabara, T., & Gage, F. H. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.112839 · Cited by 379
Cryptic and polar variation of the fragile X repeat could result in predisposing normal alleles
Kunst, C. B. (1994) · Cell · doi:10.1016/0092-8674(94)90134-1 · Cited by 363
Prevalence of carriers of premutation-size alleles of the FMRI gene--and implications for the population genetics of the fragile X syndrome.
Rousseau, F., Rouillard, P., Morel, M. L., Khandjian, E. W., & Morgan, K. (1995) · Europe PMC (PubMed Central) · Cited by 361
Translational Suppression by Trinucleotide Repeat Expansion at FMR1
Feng, Y., Zhang, F., Lokey, L. K., Chastain, J. L., Lakkis, L., Eberhart, D., & Warren, S. T. (1995) · Science · doi:10.1126/science.7732383 · Cited by 358
Self-citation
A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P
Schenck, A., Bardoni, B., Moro, A., Bagni, C., & Mandel, J.-L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151231598 · Cited by 356
The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2.
Zhang, Y., O'Connor, J. P., Siomi, M. C., Srinivasan, S., Dutra, A., Nussbaum, R. L., & Dreyfuss, G. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00220.x · Cited by 337
Phosphorylation influences the translation state of FMRP-associated polyribosomes
Ceman, S., O'Donnell, W. T., Reed, M., Patton, S., Pohl, J., & Warren, S. T. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg350 · Cited by 327
Self-citation
Trinucleotide Repeats: Mechanisms and Pathophysiology
Cummings, C. J., & Zoghbi, H. Y. (2000) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.1.1.281 · Cited by 326
Acetylated 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
Self-citation
Simple repeat DNA is not replicated simply
Richards, R. I., & Sutherland, G. R. (1994) · Nature Genetics · doi:10.1038/ng0294-114 · Cited by 310
Report of the committee on chromosome rearrangements in neoplasia and on fragile sites
Berger, R., Bloomfield, C. D., & Sutherland, G. R. (2008) · Cytogenetics and Cell Genetics · doi:10.1159/000132181 · Cited by 296
Kissing complex RNAs mediate interaction between the Fragile-X mental retardation protein KH2 domain and brain polyribosomes
Darnell, J. C., Fraser, C. E., Mostovetsky, O., Stefani, G., Jones, T. A., Eddy, S. R., & Darnell, R. B. (2005) · Genes & Development · doi:10.1101/gad.1276805 · Cited by 287
Nucleus basalis magnocellularis and hippocampus are the major sites of FMR-1 expression in the human fetal brain
Abitbol, M. M., Ménini, C., Delezoide, A., Rhyner, T. A., Vekemans, M. J. J., & Mallet, J. J. (1993) · Nature Genetics · doi:10.1038/ng0693-147 · Cited by 284
The fragile X syndrome.
Vries, B. B. A. D., Halley, D. J. J., Oostra, B. A., & Niermeijer, M. F. (1998) · Journal of Medical Genetics · doi:10.1136/jmg.35.7.579 · Cited by 262
Genetic Instabilities and Hereditary Neurological Diseases
Opal, P., & Paulson, H. L. (1998) · The American Journal of Human Genetics · doi:10.1086/302134 · Cited by 250
Localization of FMRP‐associated mRNA granules and requirement of microtubules for activity‐dependent trafficking in hippocampal neurons
Antar, L. N., Dictenberg, J. B., Plociniak, M., Afroz, R., & Bassell, G. J. (2005) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2005.00128.x · Cited by 246
Cardiovascular malformations and other cardiovascular abnormalities in neurofibromatosis 1
Lin, A. E., Birch, P. H., Korf, B. R., Tenconi, R., Niimura, M., Pöyhönen, M., Uhas, K. A., Sigorini, M., Virdis, R., Romano, C., et al. (2000) · American Journal of Medical Genetics · doi:10.1002/1096-8628(20001113)95:2 · Cited by 243
Dendritic BC1 RNA: Functional Role in Regulation of Translation Initiation
Wang, H., Iacoangeli, A., Popp, S., Muslimov, I., Imataka, H., Sonenberg, N., Lomakin, I., & Tiedge, H. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-23-10232.2002 · Cited by 232
Slippery DNA and diseases
Kunkel, T. A. (1993) · Nature · doi:10.1038/365207a0 · Cited by 222
High functioning fragile X males: Demonstration of an unmethylated fully expanded FMR‐1 mutation associated with protein expression
Hagerman, R. J., Hull, C. E., Safanda, J. F., Carpenter, I., Staley, L. W., O'Connor, R. A., Seydel, C., Mazzocco, M. M. M., Snow, K., Thibodeau, S. N., et al. (1994) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320510404 · Cited by 222
Fragile X syndrome without CCG amplification has an FMR1 deletion
Gedeon, Á. K., Baker, E., Robinson, H., Partington, M. W., Gross, B., Manca, A., Korn, B., Poustka, A., Yu, S., Sutherland, G. R., et al. (1992) · Nature Genetics · doi:10.1038/ng0892-341 · Cited by 220
Synergistic Effect of Histone Hyperacetylation and DNA Demethylation in the Reactivation of the FMR1 Gene
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
Clinical involvement and protein expression in individuals with theFMR1 premutation
Tassone, F., Hagerman, R. J., Taylor, A. K., Mills, J. B., Harris, S. W., Gane, L. W., & Hagerman, P. J. (2000) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(20000313)91:2 · Cited by 216
Histone Modifications Depict an Aberrantly Heterochromatinized FMR1 Gene in Fragile X Syndrome
Coffee, B. W., Zhang, F. P., Ceman, S., Warren, S. T., & Reines, D. (2002) · The American Journal of Human Genetics · doi:10.1086/342931 · Cited by 202
Self-citation
Immunocytochemical and Biochemical Characterization of FMRP, FXR1P, and FXR2P in the Mouse
Bakker, C. E., de Diego‐Otero, Y., Bontekoe, C. J. M., Raghoe, P., Luteijn, T., Hoogeveen, A. T., Oostra, B. A., & Willemsen, R. (2000) · Experimental Cell Research · doi:10.1006/excr.2000.4932 · Cited by 198
Alternative Splicing of Exon 14 Determines Nuclear or Cytoplasmic Localisation of FMR1 Protein Isoforms
Sittler, A., Devys, D., Weber, C., & Mandel, J.-L. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.1.95 · Cited by 198
Characterization 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
Self-citation
Heterozygous fragile X female: Historical, physical, cognitive, and cytogenetic features
Cronister, A., Schreiner, R. A., Wittenberger, M. D., Amiri, K. M. A., Harris, K., & Hagerman, R. J. (1991) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320380221 · Cited by 192
Dendritic pathology in mental retardation: from molecular genetics to neurobiology
Dierssen, M., & Ramakers, G. J. A. (2006) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2006.00224.x · Cited by 191
Fine structure of the human FMR1 gene
Eichler, E. E., Richards, S., Gibbs, R. A., & Nelson, D. L. (1993) · Human Molecular Genetics · doi:10.1093/hmg/2.8.1147 · Cited by 188
Isolation of an FMRP-Associated Messenger Ribonucleoprotein Particle and Identification of Nucleolin and the Fragile X-Related Proteins as Components of the Complex
Ceman, S., Brown, V., & Warren, S. T. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.12.7925 · Cited by 181
Self-citation
Familial transmission of the FMR1 CGG repeat.
Nolin, S. L., Lewis, F. A., Ye, L., Houck, G. E., Glicksman, A., Limprasert, P., Li, S. Y., Zhong, N., Ashley‐Koch, A. E., Feingold, E., et al. (1996) · PubMed Central · Cited by 178
Local Protein Synthesis and Spine Morphogenesis: Fragile X Syndrome and Beyond
Grossman, A. W., Aldridge, G. M., Weiler, I. J., & Greenough, W. T. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.1790-06.2006 · Cited by 177
Isolation of Sequences that Span the Fragile X and Identification of a Fragile X-Related CpG Island
Heitz, D., Rousseau, F., Devys, D., Saccone, S., Abderrahim, H., Paslier, D. L., Cohen, D., Vincent, A., Toniolo, D., Valle, G. D., et al. (1991) · Science · doi:10.1126/science.2006411 · Cited by 174
A microdeletion of less than 250 kb, including the proximal part of the FMR-I gene and the fragile-X site, in a male with the clinical phenotype of fragile-X syndrome.
Wöhrle, D., Kotzot, D., Hirst, M. C., Manca, A., Korn, B., Schmidt, A., Barbi, G., Rott, H. D., Poustka, A., & Davies, K. E. (1992) · Europe PMC (PubMed Central) · Cited by 172
Intragenic loss of function mutations demonstrate the primary role of FMR1 in fragile X syndrome
Lugenbeel, K. A., Peier, A. M., Carson, N. L., Chudley, A. E., & Nelson, D. L. (1995) · Nature Genetics · doi:10.1038/ng0895-483 · Cited by 165
The neuroanatomy and neuroendocrinology of fragile X syndrome
Hessl, D., Rivera, S. M., & Reiss, A. L. (2004) · Mental Retardation and Developmental Disabilities Research Reviews · doi:10.1002/mrdd.20004 · Cited by 165
The fragile x mental retardation protein binds and regulates a novel class of mRNAs containing u rich target sequences
Chen, L., Yun, S.-W., Seto, J., Liu, W., & Toth, M. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00406-8 · Cited by 160
Fragile X syndrome
Chudley, A. E., & Hagerman, R. J. (1987) · The Journal of Pediatrics · doi:10.1016/s0022-3476(87)80392-x · Cited by 148
Elevated Fmr1 mRNA levels and reduced protein expression in a mouse model with an unmethylated Fragile X full mutation
Brouwer, J. R., Mientjes, E., Bakker, C. E., Nieuwenhuizen, I. M., Severijnen, L.-A. W. F. M., van der Linde, H. C., Nelson, D. L., Oostra, B. A., & Willemsen, R. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.10.002 · Cited by 140
Mechanisms of premature ovarian failure.
Santoro, N. F. (2003) · PubMed · Cited by 138
Alternative splicing in the fragile X gene FMR1
Verkerk, A. J. M. H., de Graaff, E., Boulle, K. D., Eichler, E. E., Konecki, D. S., Reyniers, E., Manca, A., Poustka, A., Willems, P. J., Nelson, D. L., et al. (1993) · Human Molecular Genetics · doi:10.1093/hmg/2.8.1348 · Cited by 138
Attention and language in fragile X
Cornish, K. M., Sudhalter, V., & Turk, J. (2004) · Mental Retardation and Developmental Disabilities Research Reviews · doi:10.1002/mrdd.20003 · Cited by 136
A novel RNA binding nuclear protein that interacts with the fragile X mental retardation (FMR1) protein
Bardoni, B., Schenck, A., & Louis Mandel, J. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.13.2557 · Cited by 136
Contribution of mGluR and Fmr1 functional pathways to neurite morphogenesis, craniofacial development and fragile X syndrome
Tucker, B., Richards, R. I., & Lardelli, M. T. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl422 · Cited by 133
Down syndrome consequent to a cryptic maternal 12p;21q chromosome translocation
Scott, J. A., Wenger, S. L., Steele, M. W., & Chakravarti, A. (1995) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320560115 · Cited by 130
A deletion of 1.6 kb proximal to the CGG repeat of the FMR1 gene causes the clinical phenotype of the fragile X syndrome
Meljer, H., de Graaff, E., Merckx, D. M. L., Jongbloed, R. J. E., de Die-Smulders, C. E. M., Engelen, J. J. M., Fryns, J., Curfs, P. M. G., & Oostra, B. A. (1994) · Human Molecular Genetics · doi:10.1093/hmg/3.4.615 · Cited by 129
Cognitive decline, neuromotor and behavioural disturbances in a mouse model for fragile-X-associated tremor/ataxia syndrome (FXTAS)
Dam, D. V., Errijgers, V., Kooy, R. F., Willemsen, R., Mientjes, E., Oostra, B. A., & Deyn, P. P. D. (2005) · Behavioural Brain Research · doi:10.1016/j.bbr.2005.03.007 · Cited by 127
Methylation regulates the intracellular protein-protein and protein-RNA interactions of FMRP
Dolzhanskaya, N., Merz, G., Aletta, J. M., & Denman, R. B. (2006) · Journal of Cell Science · doi:10.1242/jcs.02882 · Cited by 119
Quantitative analysis of DNA demethylation and transcriptional reactivation of the FMR1 gene in fragile X cells treated with 5-azadeoxycytidine
Pietrobono, R. (2002) · Nucleic Acids Research · doi:10.1093/nar/gkf434 · Cited by 118
Longitudinal Changes in Cognitive and Adaptive Behavior Scores in Children and Adolescents with the Fragile X Mutation or Autism
Fisch, G. S., Simensen, R. J., & Schroer, R. J. (2002) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1014888505185 · Cited by 115
The Fragile X Site in Somatic Cell Hybrids: An Approach for Molecular Cloning of Fragile Sites
Warren, S. T., Zhang, F. P., Licameli, G. R., & Peters, J. F. (1987) · Science · doi:10.1126/science.3603029 · Cited by 111
Self-citation
Dynamic mutation: possible mechanisms and significance in human disease
Richards, R. I., & Sutherland, G. R. (1997) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(97)01108-0 · Cited by 107
The fragile X syndrome: A study of 83 families
Fryns, J. P. (1984) · Clinical Genetics · doi:10.1111/j.1399-0004.1984.tb01099.x · Cited by 102
Alternative splicing in the fragile X gene FMR1
Verkerk, A. J. M. H., de Graaff, E., Boulle, K. D., Eichler, E. E., Konecki, D. S., Reyniers, E., Manca, A., Poustka, A., Willems, P. J., Nelson, D. L., et al. (1993) · Human Molecular Genetics · doi:10.1093/hmg/2.4.399 · Cited by 101
Genetic Approaches to Molecular and Cellular Cognition: A Focus on LTP and Learning and Memory
Matynia, A., Kushner, S. A., & Silva, A. J. (2002) · Annual Review of Genetics · doi:10.1146/annurev.genet.36.062802.091007 · Cited by 99
The fragile X: a scanning electron microscope study.
Harrison, C. J., Jack, E. M., Allen, T. D., & Harris, R. (1983) · Journal of Medical Genetics · doi:10.1136/jmg.20.4.280 · Cited by 98
Clinical and molecular studies in fragile X patients with a Prader-Willi-like phenotype.
Vries, B. B. A. D., Fryns, J. P., Butler, M. G., Canziani, F., Swaay, E. W., Hemel, J. O. V., Oostra, B. A., Halley, D. J. J., & Niermeijer, M. F. (1993) · Journal of Medical Genetics · doi:10.1136/jmg.30.9.761 · Cited by 94
The N-Terminus of the Fragile X Mental Retardation Protein Contains a Novel Domain Involved in Dimerization and RNA Binding
Adinolfi, S., Ramos, A., Martin, S. R., Piaz, F. D., Pucci, P., Bardoni, B., Mandel, J., & Pastore, A. (2003) · Biochemistry · doi:10.1021/bi034909g · Cited by 92
X-linked mental retardation and verbal disability.
Rg, L. (1974) · PubMed · Cited by 85
Identification of Mouse YB1/p50 as a Component of the FMRP-Associated mRNP Particle
Ceman, S., Nelson, R., & Warren, S. T. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.4035 · Cited by 81
Self-citation
82-FIP, a novel FMRP (Fragile X Mental Retardation Protein) interacting protein, shows a cell cycle-dependent intracellular localization
Bardoni, B. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg181 · Cited by 79
Fragile X syndrome
Koekkoek, S. K. E., Yamaguchi, K., Ba, M., Dortland, B. R., Ruigrok, T. J. H., Maex, R., de Graaf, W., Ae, S., VanderWerf, F., Bakker, C. E., et al. (2005) · Cited by 75
Aortic root dilatation and mitral valve prolapse in the fragile X syndrome
Loehr, J. P., Synhorst, D. P., Wolfe, R. R., Hagerman, R. J., Opitz, J. M., & Reynolds, J. F. (1986) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320230113 · Cited by 74
Transition from premutation to full mutation in fragile X syndrome is likely to be prezygotic
Moutou, C. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.7.971 · Cited by 71
X-Linked mental retardation with fragile X. a pedigree showing transmission by apparently unaffected males and partial expression in female carriers
Nielsen, K. B., Tommerup, N., Poulsen, H., & Mikkelsen, M. (1981) · Human Genetics · doi:10.1007/bf00278849 · Cited by 71
The fragile X premutation in carriers and its effect on mutation size in offspring.
Fisch, G. S., Snow, K., Thibodeau, S. N., Chalifaux, M., Holden, J. J. A., Nelson, D. L., Howard‐Peebles, P. N., & Maddalena, A. (1995) · Europe PMC (PubMed Central) · Cited by 68
Epilepsy in fragile X syndrome
Incorpora, G., Sorge, G., Sorge, A., & Pavone, L. (2002) · Brain and Development · doi:10.1016/s0387-7604(02)00102-x · Cited by 67
An Extensive de novo deletion removing FMR1 in a patient with mental retardation and the fragile X syndrome phenotype
Tarleton, J. C., Richle, R., Schwarsz, C., Rao, K., Aylsworth, A. S., & Lachlewicz, A. (1993) · Human Molecular Genetics · doi:10.1093/hmg/2.11.1973 · Cited by 66
The fragile X-related proteins FXR1P and FXR2P contain a functional nucleolar-targeting signal equivalent to the HIV-1 regulatory proteins
Tamanini, F. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.10.1487 · Cited by 63
A Clinical and Genetic Study of 1,280 Cases of Mental Defect
(1938) · JAMA · doi:10.1001/jama.1938.02790320074036 · Cited by 63
Prenatal diagnosis of the fragile X syndrome: loss of mutation owing to a double recombinant or gene conversion event at the FMR1 locus.
Losekoot, M., Hoogendoorn, E., Olmer, R., Jansen, C. C., Oosterwijk, J., van den Ouweland, A. M., Halley, D. J. J., Warren, S. T., Willemsen, R., Oostra, B. A., et al. (1997) · Journal of Medical Genetics · doi:10.1136/jmg.34.11.924 · Cited by 62
Self-citation
The active FMR1 promoter is associated with a large domain of altered chromatin conformation with embedded local histone modifications
Gheldof, N., Tabuchi, T. M., & Dekker, J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605343103 · Cited by 61
A New DNA Marker Tightly Linked to the Fragile X Locus ( FRAXA )
Suthers, G. K., Callen, D. F., Hyland, V. J., Kozman, H. M., Baker, E. G., Eyre, H. J., Harper, P. S., Sh, R., Hors‐Cayla, M. C., Davies, K. E., et al. (1989) · Science · doi:10.1126/science.2573953 · Cited by 61
Physical mapping of new DNA probes near the fragile X mutation (FRAXA) by using a panel of cell lines.
Suthers, G., Hyland, V. J., Callen, D. F., Oberlé, I., Rocchi, M., Thomas, N. S. T., Morris, C. P., Schwartz, C. E., Schmidt, M., & Ropers, H.-H. (1990) · Europe PMC (PubMed Central) · Cited by 60
The Fragile X Syndrome
Hagerman, R. J., McBogg, P., & Hagerman, P. J. (1983) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/00004703-198306000-00009 · Cited by 56
A cerebellar tremor/ataxia syndrome among fragile X premutation carriers
Hagerman, P. J., Greco, C., & Hagerman, R. J. (2003) · Cytogenetic and Genome Research · doi:10.1159/000072856 · Cited by 48
Prenatal diagnosis of fragile X syndrome
Willemsen, R., Oosterwijk, J., Los, F. J., GALJAARD, H., & Oostra, B. A. (1996) · The Lancet · doi:10.1016/s0140-6736(05)65388-3 · Cited by 41
A YAC contig across the fragile X site defines the region of fragility
Hirst, M. C., Rack, K. A., Nakahori, Y., Roche, A., Bell, M. V., Flynn, G., Christadoulou, Z., MacKinnon, R. N., Francis, M., Littler, A. J., et al. (1991) · Nucleic Acids Research · doi:10.1093/nar/19.12.3283 · Cited by 41
The roles of Sp1, Sp3, USF1/USF2 and NRF-1 in the regulation and three-dimensional structure of the Fragile X mental retardation gene promoter
Kumari, D., Gabrielian, A. E., Wheeler, D. A., & Usdin, K. (2005) · Biochemical Journal · doi:10.1042/bj20041124 · Cited by 39
X-Linked Mental Retardation (XLMR): From Clinical Conditions to Cloned Genes
Chiurazzi, P., Tabolacci, E., & Neri, G. (2004) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408360490443013 · Cited by 37
Microsatellite DNA: a tool for population genetic analysis
Barker, G. C. (2002) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/s0035-9203(02)90047-7 · Cited by 36
The gene encoding the fragile X RNA-binding protein is controlled by nuclear respiratory factor 2 and the CREB family of transcription factors
Smith, K. T. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkj521 · Cited by 34
Human FEN-1 can process the 5'-flap DNA of CTG/CAG triplet repeat derived from human genetic diseases by length and sequence dependent manner
Lee, S., & Park, M. S. (2002) · Experimental & Molecular Medicine · doi:10.1038/emm.2002.44 · Cited by 31
The "Special Report Series" of the Medical Research Council
Bell, W. B. (1926) · BMJ · doi:10.1136/bmj.1.3408.760 · Cited by 22
Health Supervision for Children With Sickle Cell Diseases and Their Families
Committee on Genetics (1996) · PEDIATRICS · doi:10.1542/peds.98.3.467 · Cited by 12
SOTOS SYNDROME AND FRAGILE X CHROMOSOMES
Verloès, A., Sacré, J.-P., & GEUBELLE, F. (1987) · The Lancet · doi:10.1016/s0140-6736(87)90910-x · Cited by 12
Molecular diagnosis of deletions in the human multigene complex of growth and placental lactogen hormones
González-Rodríguez, E., Jaramillo‐Rangel, G., & Barrera-Saldaña, H. A. (1997) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19971112)72:4 · Cited by 10
Untitled work
Irwin (2001) · doi:10.1002/1096-8628(20010115)98:2
Untitled work
Miller (1999) · doi:10.1002/(sici)1096-8628(19990402)83:4

Research works printed but not linked: 12

Ceman S, 1999, Cell. Biol., 19, 7925
Dutch-Belgian Fragile X Consortium, 1994, Cell, 78, 23
Fisch GS, 1995, Am. J. Hum. Genet., 56, 1147
Lehrke RG, 1974, Birth Defects Orig. Artic. Ser., 10, 1
Lubs HA, 1969, Am. J. Hum. Genet., 21, 231
Martin J, 1943, Arch. Neurol. Psychiat., 6, 154
Nolin SL, 1996, Am. J. Med. Genet., 59, 1252
Penrose LS, 1938, Special Report Series, Medical Research Council 299
Rousseau F, 1995, Am. J. Hum. Genet., 57, 1006
Santoro N, 2003, Ann. Endocrinol., 64, 87
Suthers GK, 1990, Am. J. Hum. Genet., 47, 187
Wohrle D, 1992, Am. J. Hum. Genet., 51, 299

Sorted by citations

Interneuron dysfunction in psychiatric disorders
Marín, O. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3155 · Cited by 1,190
RNA-binding proteins in human genetic disease
Gebauer, F., Schwarzl, T., Valcárcel, J., & Hentze, M. W. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-00302-y · Cited by 1,208
mTOR signaling: At the crossroads of plasticity, memory and disease
Hoeffer, C. A., & Klann, E. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2009.11.003 · Cited by 1,128
Fragile X Syndrome: Loss of Local mRNA Regulation Alters Synaptic Development and Function
Bassell, G. J., & Warren, S. T. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.004 · Cited by 1,051
Self-citation
Minocycline: Far beyond an Antibiotic
Garrido‐Mesa, N., Zarzuelo, A., & Gálvez, J. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12139 · Cited by 935

See all 420

Authors: Penagarikano, O., Mulle, J. G., & Warren, S. T.
Affiliations: Department of Human Genetics, 2Department of Biochemistry and 3Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322;, ,
Emory University (US)
ORCID: Mulle, Jennifer G.
Warren, Stephen T.
Venue: Annual Review of Genomics and Human Genetics
Publisher: Annual Reviews
Published: 2007-09-01
Volume: 8
Issue: 1
Pages: 109-129
ISSN: 1527-8204 (ISSN-L)
1545-293X
DOI: 10.1146/annurev.genom.8.080706.092249
OpenAlex: W2141296384
Cited by: 420
References: 133
Citations by year: 2026: 13 · 2025: 12 · 2024: 10 · 2023: 11 · 2022: 11 · 2021: 19 · 2020: 14 · 2019: 26 · 2018: 21 · 2017: 20 · 2016: 24 · 2015: 24 · 2014: 32 · 2013: 27 · 2012: 39
FWCI: 2.97
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Genomics and Human Genetics (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: fragile X syndrome, FMR1 gene, CGG repeat expansion, FMRP, RNA-binding proteins, translational regulation, synaptic plasticity, dendritic mRNA localization, epigenetic silencing, hypermethylation, intellectual disability, pathophysiology, pharmacological interventions
MeSH terms: Base Sequence, Fragile X Syndrome, Humans, Models, Biological, Molecular Sequence Data, Mutation, Neurons, Nucleic Acid Conformation, Trinucleotide Repeats, Inheritance Patterns, Chromosomes, Human, X, Fragile X Messenger Ribonucleoprotein 1

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.

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

The Pathophysiology of Fragile X Syndrome

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks