title: The full mutation in the FMR-1 gene of male fragile X patients is absent in their sperm.
abstract: Fragile X syndrome is characterized at the molecular level by amplification of a (CGG)n repeat and hypermethylation of a CpG island preceeding the open reading frame of the fragile X gene (FMR-1) located in Xq27.3. Anticipation in this syndrome is associated with progressive amplification of the (CGG)n repeat from a premutation to a full mutation through consecutive generations. Remarkably, expansion of the premutation to the full mutation is strictly maternal. To clarify this parental influence we studied FMR-1 in sperm of four male fragile X patients. This showed that only the premutation was present in their sperm, although they had a full mutation in peripheral lymphocytes. This might suggest that expansion of the premutation to the full mutation in FMR-1 does not occur in meiosis but in a postzygotic stage.
authors.affiliation: Department of Medical Genetics, University of Antwerp-ULA, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Reyniers
authors.forename: L
authors.initials: L
authors.lastname: Vits
authors.forename: K
authors.initials: K
authors.lastname: De Boulle
authors.forename: B
authors.initials: B
authors.lastname: Van Roy
authors.forename: D
authors.initials: D
authors.lastname: Van Velzen
authors.forename: E
authors.initials: E
authors.lastname: de Graaff
authors.forename: A J
authors.initials: AJ
authors.lastname: Verkerk
authors.forename: H Z
authors.initials: HZ
authors.lastname: Jorens
authors.forename: J K
authors.initials: JK
authors.lastname: Darby
authors.forename: B
authors.initials: B
authors.lastname: Oostra
mesh_terms: D004252:DNA Mutational Analysis; D005314:Embryonic and Fetal Development / Q000235:genetics; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D005784:Gene Amplification; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D008540:Meiosis; D008745:Methylation; D008957:Models, Genetic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins; D012091:Repetitive Sequences, Nucleic Acid; D012727:Sex Characteristics; D013094:Spermatozoa / Q000737:chemistry*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human