Mandel Jean-Louis, Chelly Jamel
Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC) (CNRS/INSERM/Université Louis Pasteur, Collège de France), 67404 Illkirch/CU Strasbourg, France.
Eur J Hum Genet. 2004 Sep;12(9):689-93. doi: 10.1038/sj.ejhg.5201247.
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.
智力迟钝在男性中的发病率比女性高30%至50%，而X连锁智力迟钝（XLMR）被认为是这种性别差异的主要原因。非综合征性XLMR非常异质，迄今为止已鉴定出15多个基因，每个基因在非综合征性家族中所占比例都非常小。无尾X（ARX）基因是个例外，因为在136个此类家族中的11个中发现了该基因突变，一种高度复发性突变（dup24）导致蛋白质中聚丙氨酸序列的扩展。在明确的X连锁智力迟钝家族中报道的dup24频率相当高（6.6%），与此形成对比的是，在散发性男性智力迟钝中观察到的这种突变的患病率非常低（0.13%）。我们得出结论，单基因XLMR在男性智力迟钝中的患病率远低于10%，而要解释智力迟钝男性比女性多30%的情况，则需要23%的患病率。
