Romero-Rubio M T, Andrés-Celma M, Castelló-Pomares M L, Roselló M, Ferrer-Bolufer I, Martínez-Castellano F
Hospital Clínico Universitario, Valencia, España.
Rev Neurol. 2008;47(12):634-7.
Mental retardation has an approximated prevalence of 2% in the general population and its most frequent cause is X-fragile syndrome. This genetic disorder predominantly affects males and it is mainly caused by the expansion of CGG in FMR1 gene. Recently has been demonstrated that mutations in a new called ARX gene (aristaless-related homeobox) can also cause a similar form of X linked mental retardation, as well as other neurological disorders (autism, Partington or West syndrome). The most frequent mutation that has been reported is the c.428_451 dup24, which comprises almost 60% of all described. It causes an expansion of a polyalanine tract of ARX protein.
We report three cases of mental retardation in two different families where the mutation in ARX gene c.428_451 dup24 was found while X-fragile syndrome screening was made. Personal and familiar history, phenotype and evolution are described.
The molecular analysis of this mutation should be considered as a routine for the genetic diagnosis of mental retardation in males of nondrafted cause.
智力迟钝在普通人群中的患病率约为2%，其最常见的病因是脆性X综合征。这种遗传性疾病主要影响男性，主要由FMR1基因中CGG的扩增引起。最近已证实，一种名为ARX基因（无触角相关同源框）的新基因突变也可导致类似形式的X连锁智力迟钝，以及其他神经系统疾病（自闭症、帕廷顿或韦斯特综合征）。已报道的最常见突变是c.428_451 dup24，几乎占所有已描述突变的60%。它导致ARX蛋白的聚丙氨酸序列扩增。
我们报告了两个不同家庭中的三例智力迟钝病例，在进行脆性X综合征筛查时发现了ARX基因c.428_451 dup24突变。描述了个人和家族史、表型及病情发展。
对于不明原因智力迟钝男性的基因诊断，应将该突变的分子分析作为常规检查。
