title: Physical mapping across the fragile X: hypermethylation and clinical expression of the fragile X syndrome.
abstract: The most common genetic cause of mental retardation after Down's syndrome, the fragile X syndrome, is associated with the occurrence of a fragile site at Xq27.3. This X-linked disease is intriguing because transmission can occur through phenotypically normal males. Theories to explain this unusual phenomenon include genomic rearrangements and methylation changes associated with a local block of reactivation of the X chromosome. Using microdissected markers close to the fragile site, we have been able to test these hypotheses. We present evidence for the association of methylation with the expression of the disease. However, there is no simple relationship between the degree of methylation and either the level of expression of the fragile site or the severity of the clinical phenotype.
authors.affiliation: Molecular Genetics Group, John Radcliffe Hospital, Oxford, England.
authors.forename: M V
authors.initials: MV
authors.lastname: Bell
authors.forename: M C
authors.initials: MC
authors.lastname: Hirst
authors.forename: Y
authors.initials: Y
authors.lastname: Nakahori
authors.forename: R N
authors.initials: RN
authors.lastname: MacKinnon
authors.forename: A
authors.initials: A
authors.lastname: Roche
authors.forename: T J
authors.initials: TJ
authors.lastname: Flint
authors.forename: P A
authors.initials: PA
authors.lastname: Jacobs
authors.forename: N
authors.initials: N
authors.lastname: Tommerup
authors.forename: L
authors.initials: L
authors.lastname: Tranebjaerg
authors.forename: U
authors.initials: U
authors.lastname: Froster-Iskenius
mesh_terms: D002460:Cell Line; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005600:Fragile X Syndrome / Q000235:genetics*; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008745:Methylation; D015183:Restriction Mapping; D014960:X Chromosome
chemical_list: D004247:DNA