A point mutation in the FMR-1 gene associated with fragile X mental retardation

Kristel De Boulle, Annemieke J.M.H. Verkerk, Edwin Reyniers, Lieve Vits, Jan Hendrickx, Bernadette Van Roy, Feikje Van Den Bos, Esther de Graaff, Ben A. Oostra, Patrick J. Willems*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

525 Citations (Scopus)


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 Ne367Asn 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.

Original languageEnglish
Pages (from-to)31-35
Number of pages5
JournalNature Genetics
Issue number1
Publication statusPublished - 1 Jan 1993


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