title: A point mutation in the FMR-1 gene associated with fragile X mental retardation.
abstract: The vast majority of patients with fragile X syndrome show a folate-sensitive fragile site at Xq27.3 (FRAXA) at the cytogenetic level, and both amplification of the (CGG)n repeat and hypermethylation of the CpG island in the 5' fragile X gene (FMR-1) at the molecular level. We have studied the FMR-1 gene of a patient with the fragile X phenotype but without cytogenetic expression of FRAXA, a (CGG)n repeat of normal length and an unmethylated CpG island. We find a single point mutation in FMR-1 resulting in an lle367Asn substitution. This de novo mutation is absent in the patient's family and in 130 control X chromosomes, suggesting that the mutation causes the clinical abnormalities. Our results suggest that mutations in FMR-1 are directly responsible for fragile X syndrome, irrespective of possible secondary effects caused by FRAXA.
authors: Department of Medical Genetics, University of Antwerp-UIA, Belgium.
authors: K
authors: K
authors: De Boulle
authors: A J
authors: AJ
authors: Verkerk
authors: E
authors: E
authors: Reyniers
authors: L
authors: L
authors: Vits
authors: J
authors: J
authors: Hendrickx
authors: B
authors: B
authors: Van Roy
authors: F
authors: F
authors: Van den Bos
authors: E
authors: E
authors: de Graaff
authors: B A
authors: BA
authors: Oostra
authors: P J
authors: PJ
authors: Willems
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D002461:Cell Line, Transformed; D004247:DNA; D004252:DNA Mutational Analysis; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D004247:DNA; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human