Proposed mechanism of inheritance and expression of the human fragile-X syndrome of mental retardation - PubMed (original) (raw)
Proposed mechanism of inheritance and expression of the human fragile-X syndrome of mental retardation
C D Laird. Genetics. 1987 Nov.
Abstract
A mechanism is proposed for the inheritance and expression of the fragile-X-linked syndrome of mental retardation in humans. Two independent events are required for expression of the syndrome: the fragile-X mutation, and X chromosome inactivation in pre-oogonial cells. The fragile-X mutation at site Xq27 has little or no effect until the chromosome is inactivated in a female as part of the process of dosage compensation. At a stage where the inactivated X chromosome would normally be reactivated in preparation for oogenesis, the mutation results in a local block to the reactivation process. This block to reactivation leads to mental retardation in progeny by reducing the level of products from the unreactivated Xq27 region in male cells, and, for a heterozygous female, in somatic cells in which the normal X chromosome has been inactivated. Published data relevant to this proposed mechanism are discussed.
Similar articles
- Two progenitor cells for human oogonia inferred from pedigree data and the X-inactivation imprinting model of the fragile-X syndrome.
Laird CD, Lamb MM, Thorne JL. Laird CD, et al. Am J Hum Genet. 1990 Apr;46(4):696-719. Am J Hum Genet. 1990. PMID: 1969225 Free PMC article. - Study of a family with a fragile site of the X chromosome at Xq27-28 without mental retardation.
Voelckel MA, Philip N, Piquet C, Pellissier MC, Oberlé I, Birg F, Mattei MG, Mattei JF. Voelckel MA, et al. Hum Genet. 1989 Mar;81(4):353-7. doi: 10.1007/BF00283690. Hum Genet. 1989. PMID: 2564838 - A premutation that generates a defect at crossing over explains the inheritance of fragile X mental retardation.
Pembrey ME, Winter RM, Davies KE. Pembrey ME, et al. Am J Med Genet. 1985 Aug;21(4):709-17. doi: 10.1002/ajmg.1320210413. Am J Med Genet. 1985. PMID: 4040705 - The fragile X syndrome.
Brown WT. Brown WT. Neurol Clin. 1989 Feb;7(1):107-21. Neurol Clin. 1989. PMID: 2646518 Review. - [Mental retardation linked to fragility of chromosome X: current knowledge].
Mattei JF, Mattei MG, Auger M, Giraud F. Mattei JF, et al. J Genet Hum. 1984 Jul;32(3):167-92. J Genet Hum. 1984. PMID: 6237176 Review. French.
Cited by
- Genomic imprinting and position-effect variegation in Drosophila melanogaster.
Lloyd VK, Sinclair DA, Grigliatti TA. Lloyd VK, et al. Genetics. 1999 Apr;151(4):1503-16. doi: 10.1093/genetics/151.4.1503. Genetics. 1999. PMID: 10101173 Free PMC article. - The Contribution of Somatic Expansion of the CAG Repeat to Symptomatic Development in Huntington's Disease: A Historical Perspective.
Monckton DG. Monckton DG. J Huntingtons Dis. 2021;10(1):7-33. doi: 10.3233/JHD-200429. J Huntingtons Dis. 2021. PMID: 33579863 Free PMC article. Review. - Molecular cloning and analysis of the fragile X region in man.
Dietrich A, Kioschis P, Monaco AP, Gross B, Korn B, Williams SV, Sheer D, Heitz D, Oberle I, Toniolo D, et al. Dietrich A, et al. Nucleic Acids Res. 1991 May 25;19(10):2567-72. doi: 10.1093/nar/19.10.2567. Nucleic Acids Res. 1991. PMID: 2041732 Free PMC article. - The fragile X mutation does not have any major effect on the expression of the hypoxanthine phosphoribosyltransferase (HPRT) locus in human fibroblasts.
Steen AM, Marcus S, Sahlén S, Nielsen KB, Lambert B. Steen AM, et al. Hum Genet. 1991 Aug;87(4):503-5. doi: 10.1007/BF00197177. Hum Genet. 1991. PMID: 1715310 - Prevalence of carriers of premutation-size alleles of the FMRI gene--and implications for the population genetics of the fragile X syndrome.
Rousseau F, Rouillard P, Morel ML, Khandjian EW, Morgan K. Rousseau F, et al. Am J Hum Genet. 1995 Nov;57(5):1006-18. Am J Hum Genet. 1995. PMID: 7485149 Free PMC article.
References
- Am J Hum Genet. 1983 Sep;35(5):861-8 - PubMed
- Science. 1975 Jan 24;187(4173):226-32 - PubMed
- Ann N Y Acad Sci. 1986;477:129-50 - PubMed
- Am J Hum Genet. 1981 Sep;33(5):752-61 - PubMed
- Genetics. 1960 Oct;45(10):1429-43 - PubMed
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Medical