title: Fragile-X syndrome: unique genetics of the heritable unstable element.
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.affiliation: Department of Cytogenetics and Molecular Genetics, Adelaide Children's Hospital, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Yu
authors.forename: J
authors.initials: J
authors.lastname: Mulley
authors.forename: D
authors.initials: D
authors.lastname: Loesch
authors.forename: G
authors.initials: G
authors.lastname: Turner
authors.forename: A
authors.initials: A
authors.lastname: Donnelly
authors.forename: A
authors.initials: A
authors.lastname: Gedeon
authors.forename: D
authors.initials: D
authors.lastname: Hillen
authors.forename: E
authors.initials: E
authors.lastname: Kremer
authors.forename: M
authors.initials: M
authors.lastname: Lynch
authors.forename: M
authors.initials: M
authors.lastname: Pritchard
mesh_terms: D015139:Blotting, Southern; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics*; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008745:Methylation; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D014960:X Chromosome
chemical_list: C024388:CTGCAG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific