Cited by 2,080Genetics and Neurodevelopmental DisordersGenetic Neurodegenerative DiseasesGenetic factors in colorectal cancer

Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox

Fu, Ying-Hui, Kuhl, Derek P.A., Pizzuti, Antonio, Pieretti, Maura, Sutcliffe, James S., Richards, Stephen, Verkert, Annemieke J.M.H., Holden, Jeanette J.A. +5 more·1991·Cell

Abstract

Fragile X syndrome results from mutations in a (CGG)n repeat found in the coding sequence of the FMR-1 gene. Analysis of length variation in this region in normal individuals shows a range of allele sizes varying from a low of 6 to a high of 54 repeats. Premutations showing no phenotypic effect in fragile X families range in size from 52 to over 200 repeats. All alleles with greater than 52 repeats, including those identified in a normal family, are meiotically unstable with a mutation frequency of one, while 75 meioses of alleles of 46 repeats and below have shown no mutation. Premutation alleles are also mitotically unstable as mosaicism is observed. The risk of expansion during oogenesis to the full mutation associated with mental retardation increases with the number of repeats, and this variation in risk accounts for the Sherman paradox.

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Crossref · 10.1016/0092-8674(91)90283-5

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  • Fragile X syndrome is caused by mutations in FMR1, which lies on the X chromosome at Xq27.3 and coincides with the folate-sensitive fragile site.

    “FXS is caused by mutations in the FMR1 gene, which is located on the X chromosome and whose locus at Xq27.3 coincides with the folate-sensitive fragile site (4, 5).”

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Authors
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., Oostra, B. A., Nelson, D. L., & Caskey, C. T.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Queen's University (CA)
Venue
Cell
Publisher
Elsevier BV
Published
1991-12
Volume
67
Issue
6
Pages
1047-1058
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2167119720
Cited by
2,080
References
25
Citations by year
2026: 12 · 2025: 23 · 2024: 36 · 2023: 22 · 2022: 31 · 2021: 41 · 2020: 43 · 2019: 37 · 2018: 49 · 2017: 34 · 2016: 65 · 2015: 56 · 2014: 78 · 2013: 68 · 2012: 70
FWCI
58.19
Type
journal article
Language
en
Open access
closed
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Human Genome Research Institute (HG00038)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 20521)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords
fragile X syndrome, CGG repeat, FMR1 gene, premutation, repeat expansion, meiotic instability, mitotic instability, mosaicism, repeat length variation, oogenesis, intellectual disability
MeSH terms
Alleles, Base Sequence, Exons, Fragile X Syndrome, Genes, Humans, Meiosis, Methylation, Molecular Sequence Data, Mosaicism, Oligodeoxyribonucleotides, Pedigree, Polymorphism, Genetic, Repetitive Sequences, Nucleic Acid, Risk Factors, X Chromosome, Restriction Mapping, Polymerase Chain Reaction

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