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

Nature Genetics volume 3, pages 31–35 (1993)Cite this article

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 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

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Authors and Affiliations

  1. Department of Medical Genetics, University of Antwerp-UIA, Universiteitsplein 1, 2610, Antwerp, Belgium

    Kristel De Boulle, Edwin Reyniers, Lieve Vits, Jan Hendrickx, Bernadette Van Roy & Patrick J. Willems

  2. Department of Clinical Genetics, Erasmus University, Dr Molewaterplein 50, 3153 DR, Rotterdam, The Netherlands

    Annemieke J.M.H. Verkerk & Esther de Graaff

  3. Institute of Mentally Retarded Het Bouwhuis, Welnaweg 100, 7542 AK, Enschede, The Netherlands

    Feikje Van Den Bos

  4. Department of Cell Biology, Erasmus University, Dr Molewaterplein 50, 3153 DR, Rotterdam, The Netherlands

    Ben A. Oostra

Authors
  1. Kristel De Boulle
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  2. Annemieke J.M.H. Verkerk
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  3. Edwin Reyniers
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  4. Lieve Vits
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  9. Ben A. Oostra
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  10. Patrick J. Willems
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De Boulle, K., Verkerk, A., Reyniers, E. et al. A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nat Genet 3, 31–35 (1993). https://doi.org/10.1038/ng0193-31

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