Fragile-X syndrome: Unique genetics of the heritable unstable element

S. Yu, J. Mulley, D. Loesch, G. Turner, A. Donnelly, A. Gedeon, D. Hillen, E. Kremer, M. Lynch, M. Pritchard, G. R. Sutherland, R. I. Richards

Research output: Contribution to journalArticlepeer-review

180 Citations (Scopus)


The fragile site at Xq27.3 is an unstable microsatellite repeat, p(CCG)(n). In fragile-X syndrome pedigrees, this sequence exhibits variable amplification, the length of which correlates with fragile-site expression. There is a direct relationship between increased p(CCG)(n) copy number and propensity for instability: individuals having large amplifications exhibit somatic variation due to increased instability. The instability of the p(CCG)(n) repeat, when transmitted through affected pedigrees, explains the unusual segregation patterns of fragile-X phenotype, referred to as the Sherman paradox. All individuals of fragile-X genotype were found (where testing was possible) to have a parent with amplified p(CCG)(n) repeat, indicating that few, if any, cases of fragile-X syndrome are not familial.

Original languageEnglish
Pages (from-to)968-980
Number of pages13
JournalAmerican Journal of Human Genetics
Issue number5
Publication statusPublished - 1 Jun 1992
Externally publishedYes


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