A gene for nonspecific mental retardation is localized to Xp22.2-p21.2 in a Belgian family
- Univ. of Leuven (Belgium); and others
We report a family with 6 male individuals with moderate mental retardation (MR) and a nonspecific phenotype, one additional male individual with borderline to mild MR and two obligate female carriers with borderline MR. All family members tested were negative for the fragile X MR mutation. In order to localize the MR gene on the X chromosome, we used 16 highly polymorphic markers dispersed over the whole X-chromosome. Under the model of full penetrance in males and 20% penetrance in carrier females, moderate positive peak lod scores of 0.90 at 10%, 1.14 at 20% and 1.17 at 18% recombination were obtained with DXS999, DXS989 and DMD49, respectively. Al three markers are located in Xp22.2-p21.2. With markers located distal of DXS999, proximal of DMD49 and on Xq, close linkage in this family could be rejected. In multipoint linkage analysis, distinct negative lod scores were obtained in all intervals between markers proximal of Xp21 and on Xq. On the other hand, a disappointing peak lod score of 0.69 was obtained between DXS989 and DMD. This lod score by itself is not significant to justify definite localization of the MR gene in this chromosomal region. However, taken into account the exclusion data in other regions on the X-chromosome, the odds in favor of positioning the MR gene between DXS989 and DMD versus regions proximal of DMD49 are at least 160 to 1. The low peak lod score is explained by the inheritance of a different Xp haplotype in the borderline to mild mentally retarded male patient compared to his two affected brothers and his two carrier sisters. Linkage analysis in other families with nonspecific MR have suggested the existence of MR genes in Xp22.3-p22.2 (MRX2) and Xq21-q21 (MRX5, 10, 11, 12, 13). As these partially overlapping localizations have been obtained with different markers, it is not clear whether these families represent one single MR syndrome.
- OSTI ID:
- 134716
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-1454
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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