title: Rare variants in the promoter of the fragile X syndrome gene (FMR1).
abstract: Fragile X syndrome, the most common form of familial mental retardation, is mainly caused by the expansion of an unstable region of CGG repeats in the 5' untranslated region of the FMR1 (Fragile X Mental Retardation-1) gene. Molecular tools to detect an abnormal CGG expansion in FMR1 include Southern blot hybridization and PCR amplification. Southern blotting with the StB12.3 probe and Eco RI/Eag I double digestion is widely used as a routine test for fragile X syndrome diagnosis in laboratories around the world. A patient with mental retardation of unknown origin showed absence of digestion for Eag I due to a -149C-->G substitution in the CpG island of the FMR1 gene, which destroys that restriction enzyme site. Screening for other changes around that region also detected a -154insGGC in a patient with a phenotype highly suggestive of fragile X syndrome but without CGG expansion. Expression studies did not show any abnormal changes in FMR1 function. In summary, we have identified two different changes (a C to G substitution at -149 and a GGC insertion at -154) in the promoter of the FMR1 gene. These are the first variants described in the promoter of the FMR1 gene.
authors.affiliation: Servei de Genètica, Hospital Clínic, Barcelona, Catalunya, Spain. montse@medicina.ub.es
authors.forename: M
authors.initials: M
authors.lastname: Milà
authors.forename: S
authors.initials: S
authors.lastname: Castellví-Bel
authors.forename: A
authors.initials: A
authors.lastname: Sánchez
authors.forename: A
authors.initials: A
authors.lastname: Barceló
authors.forename: C
authors.initials: C
authors.lastname: Badenas
authors.forename: J
authors.initials: J
authors.lastname: Mallolas
authors.forename: X
authors.initials: X
authors.lastname: Estivill
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D018899:CpG Islands; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D017930:Genes, Reporter; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D018911:Trinucleotide Repeats
chemical_list: D015252:Deoxyribonucleases, Type II Site-Specific; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; C497683:FMR1 protein, human; C046751:endodeoxyribonuclease XmaIII