151. A point mutation in the FMR-1 gene associated with fragile X mental retardation.
- Author
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De Boulle K, Verkerk AJ, Reyniers E, Vits L, Hendrickx J, Van Roy B, Van den Bos F, de Graaff E, Oostra BA, and Willems PJ
- Subjects
- Adult, Amino Acid Sequence, Base Sequence, Blotting, Southern, Cell Line, Transformed, DNA, DNA Mutational Analysis, Female, Fragile X Mental Retardation Protein, Humans, Male, Molecular Sequence Data, Pedigree, Polymerase Chain Reaction, RNA, Messenger analysis, Repetitive Sequences, Nucleic Acid, Fragile X Syndrome genetics, Nerve Tissue Proteins genetics, Point Mutation, RNA-Binding Proteins
- 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.
- Published
- 1993
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