title: Linkage analysis of the fragile X gene FMR-1 and schizophrenia: no evidence for linkage but report of a family with schizophrenia and an unstable triplet repeat.
abstract: We have examined 23 families multiply affected with schizophrenia for linkage to the FMR-1 gene on the X chromosome. Alleles at the FMR-1 CGG triplet repeat were analysed by the polymerase chain reaction, and methylation status at the FMR-1 locus in individuals with evidence of expanded or unstable repeats was analysed by Southern hybridization. Two-point LOD score analyses with a range of X-linked single gene models and a non-parametric affected sib-pair method revealed no evidence for linkage. In one family, however, a fragile X premutation was found, and one individual with schizophrenia and developmental delay was a mosaic for the full and premutation. We conclude that although mutations within the FMR-1 gene do not have a major aetiological role in schizophrenia in our collection of pedigrees, it is possible that FMR-1 mutations can modify the clinical phenotype of schizophrenia.
authors.affiliation: Institute of Psychiatry, Department of Psychological Medicine, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Ashworth
authors.forename: I
authors.initials: I
authors.lastname: Abusaad
authors.forename: C
authors.initials: C
authors.lastname: Walsh
authors.forename: S
authors.initials: S
authors.lastname: Nanko
authors.forename: R M
authors.initials: RM
authors.lastname: Murray
authors.forename: P
authors.initials: P
authors.lastname: Asherson
authors.forename: P
authors.initials: P
authors.lastname: McGuffin
authors.forename: M
authors.initials: M
authors.lastname: Gill
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
authors.forename: D A
authors.initials: DA
authors.lastname: Collier
mesh_terms: D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000453:epidemiology / Q000235:genetics*; D005799:Genes, Dominant; D005808:Genes, Recessive; D008040:Genetic Linkage; D006801:Humans; D007231:Infant, Newborn; D008126:Lod Score; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009771:Obsessive-Compulsive Disorder / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011618:Psychotic Disorders / Q000235:genetics; D016601:RNA-Binding Proteins; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D018911:Trinucleotide Repeats
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human