Monogenic X-linked mental retardation: Is it as frequent as currently estimated? The paradox of the ARX (Aristaless X) mutations

被引:86
作者
Mandel, JL [1 ]
Chelly, J
机构
[1] Univ Strasbourg 1, Coll France, IGBMC, CNRS,INSERM, F-67404 Strasbourg, France
[2] Univ Paris 05, CNRS, INSERM, Inst Cochin Genet Mol, F-75270 Paris, France
[3] Ctr Hosp Univ Strasbourg, Strasbourg, France
关键词
D O I
10.1038/sj.ejhg.5201247
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mental retardation affects 30 to 50% more males than females, and X-linked mental retardation (XLMR) is thought to account for the major part of this sex bias. Nonsyndromic XLMR is very heterogeneous, with more than 15 genes identified to date, each of them accounting for a very small proportion of nonsyndromic families. The Aristaless X (ARX) gene is an exception since it was found mutated in 11 of 136 such families, with a highly recurrent mutation (dup24) leading to an expansion of a polyalanine tract in the protein. The rather high frequency of dup24 reported in families with clear X-linked MR (6.6%) contrasts with the very low prevalence of this mutation observed in sporadic male MR (0.13%). We conclude that monogenic XLMR has much lower prevalence in male MR (<10%) than the 23% that would be required to account for a 30% male excess of mental retardation.
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页码:689 / 693
页数:5
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