title: Mutational analysis of the FMR1 gene in 118 mentally retarded males suspected of fragile X syndrome: absence of prevalent mutations.
abstract: Fragile X syndrome is usually caused by expansion of a trinucleotide (CGG) repeat in the 5'-untranslated region of the FMR1 gene. However, both deletions and point mutations in FMR1 have been identified as rare causes of the fragile X syndrome. We have screened the FMR1 gene for mutations by single-stranded conformational polymorphism analysis in 118 mentally retarded males who were referred to us for fragile X testing, and who had a CGG repeat number in the normal size range. We found one patient with a 2-bp deletion in intron 1 and two unrelated patients with identical silent mutations in exon 1. Neither of these mutations were found in 83 controls. Further investigation of the exon 1 silent mutation by Western blot analysis showed normal expression of FMRP in lymphoblastoid cells and reverse-transcription-polymerase chain reaction analysis showed that intron 1 and 2 were spliced out as in the normal control. Furthermore, we found two common polymorphisms, one in intron 1 and one in exon 5. However, no pathogenic FMR1 mutation was found.
authors.affiliation: Department of Medical Genetics, The John F. Kennedy Institute, Glostrup, Denmark. kag@jfk.kennedy.dk
authors.forename: K
authors.initials: K
authors.lastname: Grønskov
authors.forename: A
authors.initials: A
authors.lastname: Hallberg
authors.forename: K
authors.initials: K
authors.lastname: Brøndum-Nielsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D016601:RNA-Binding Proteins; D013737:Testis / Q000002:abnormalities
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human