Fragile-X syndrome: Unique genetics of the heritable unstable element |
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| Authors: | 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 |
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| Affiliation: | Department of Cytogenetics and Molecular Genetics, Adelaide Children's Hospital, Australia. |
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| Abstract: | 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. |
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