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

Fu YH, Kuhl DP, Pizzuti A, Pieretti M, Sutcliffe JS, Richards S, Verkerk AJ, Holden JJ, Fenwick RG, Warren ST
Cell. 1991 67 (6): 1047-58

PMID: 1760838 · DOI:10.1016/0092-8674(91)90283-5

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.

MeSH Terms (18)

Alleles Base Sequence Exons Fragile X Syndrome Genes Humans Meiosis Methylation Molecular Sequence Data Mosaicism Oligodeoxyribonucleotides Pedigree Polymerase Chain Reaction Polymorphism, Genetic Repetitive Sequences, Nucleic Acid Restriction Mapping Risk Factors X Chromosome

Connections (1)

This publication is referenced by other Labnodes entities:

Links