A point mutation in the FMR-1 gene associated with fragile X mental retardation - PubMed (original) (raw)
Case Reports
doi: 10.1038/ng0193-31.
Affiliations
- PMID: 8490650
- DOI: 10.1038/ng0193-31
Case Reports
A point mutation in the FMR-1 gene associated with fragile X mental retardation
K De Boulle et al. Nat Genet. 1993 Jan.
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.
Similar articles
- The full mutation in the FMR-1 gene of male fragile X patients is absent in their sperm.
Reyniers E, Vits L, De Boulle K, Van Roy B, Van Velzen D, de Graaff E, Verkerk AJ, Jorens HZ, Darby JK, Oostra B, et al. Reyniers E, et al. Nat Genet. 1993 Jun;4(2):143-6. doi: 10.1038/ng0693-143. Nat Genet. 1993. PMID: 8348152 - [Detection of FMR-1 gene expression by RT-PCR].
Zheng L, Fan Y, Huang T, Zhu N, Shen Y, Wu G. Zheng L, et al. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1995 Dec;17(6):407-11. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1995. PMID: 9208564 Chinese. - Characterization and localization of the FMR-1 gene product associated with fragile X syndrome.
Verheij C, Bakker CE, de Graaff E, Keulemans J, Willemsen R, Verkerk AJ, Galjaard H, Reuser AJ, Hoogeveen AT, Oostra BA. Verheij C, et al. Nature. 1993 Jun 24;363(6431):722-4. doi: 10.1038/363722a0. Nature. 1993. PMID: 8515814 - Molecular analysis of the fragile X syndrome.
Knight SJ, Hirst MC, Davies KE. Knight SJ, et al. Dis Markers. 1992 Jan-Feb;10(1):1-5. Dis Markers. 1992. PMID: 1424438 Review. - Molecular pathology of the fragile X syndrome.
Tsongalis GJ, Silverman LM. Tsongalis GJ, et al. Arch Pathol Lab Med. 1993 Nov;117(11):1121-5. Arch Pathol Lab Med. 1993. PMID: 8239933 Review.
Cited by
- The new (dis)order in RNA regulation.
Järvelin AI, Noerenberg M, Davis I, Castello A. Järvelin AI, et al. Cell Commun Signal. 2016 Apr 6;14:9. doi: 10.1186/s12964-016-0132-3. Cell Commun Signal. 2016. PMID: 27048167 Free PMC article. Review. - Genome-wide analysis validates aberrant methylation in fragile X syndrome is specific to the FMR1 locus.
Alisch RS, Wang T, Chopra P, Visootsak J, Conneely KN, Warren ST. Alisch RS, et al. BMC Med Genet. 2013 Jan 29;14:18. doi: 10.1186/1471-2350-14-18. BMC Med Genet. 2013. PMID: 23356558 Free PMC article. - The unstable repeats--three evolving faces of neurological disease.
Nelson DL, Orr HT, Warren ST. Nelson DL, et al. Neuron. 2013 Mar 6;77(5):825-43. doi: 10.1016/j.neuron.2013.02.022. Neuron. 2013. PMID: 23473314 Free PMC article. Review. - Cellular and synaptic network defects in autism.
Peça J, Feng G. Peça J, et al. Curr Opin Neurobiol. 2012 Oct;22(5):866-72. doi: 10.1016/j.conb.2012.02.015. Epub 2012 Mar 20. Curr Opin Neurobiol. 2012. PMID: 22440525 Free PMC article. Review. - The RNA-binding protein FMRP facilitates the nuclear export of _N_6-methyladenosine-containing mRNAs.
Hsu PJ, Shi H, Zhu AC, Lu Z, Miller N, Edens BM, Ma YC, He C. Hsu PJ, et al. J Biol Chem. 2019 Dec 27;294(52):19889-19895. doi: 10.1074/jbc.AC119.010078. Epub 2019 Nov 21. J Biol Chem. 2019. PMID: 31753916 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases