Fragile-X syndrome: Unique genetics of the heritable unstable element Academic Article uri icon

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.

authors

  • Yu, S
  • Mulley, J
  • Loesch, D
  • Turner, G
  • Donnelly, A
  • Gedeon, A
  • Hillen, D
  • Kremer, E
  • Lynch, M
  • Pritchard, M
  • Sutherland, GR
  • Richards, RI

publication date

  • June 1, 1992