X-linked mild non-syndromic mental retardation with neuropsychiatric problems and the missense mutation A365E in PAK3
X-linked mild non-syndromic mental retardation with neuropsychiatric problems and the missense mutation A365E in PAK3
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DOI：
10.1002/ajmg.a.20131
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发表时间：
2003-08-01
影响因子：
2
通讯作者：
Mulley, JC
中科院分区：
文献类型：
--
作者：
Gedeon, AK;Nelson, J;Mulley, JC
我们描述了一个由 19 名男性组成的家庭，共 5 代，患有轻度至边缘性非综合征性 X 连锁智力低下 (MRX)。受影响的男性除了精神障碍和耳朵相对较长外，没有其他临床表现，部分病例还存在神经精神问题。使用跨越 X 染色体的 34 个标记对部分谱系进行连锁分析，将基因定位在 Xq23 中的 DXS454 和 DXS1001 之间。 DXS1059 的最大两点 lod 得分为 3.21。 PAK3 是映射到同一区域的已知 MRX 基因。发现受影响的雄性和专性携带者雌性有错义突变c。外显子 10 中的 1094C > A 导致蛋白质高度保守区域发生 A365E 取代。 C 碱基变为 A 碱基，废除了 PvuII 限制性内切酶位点，为大家庭中的携带者检测和产前诊断（如果需要）提供了简单测试的基础。 (C) 2003 Wiley-Liss, Inc.
We describe a family of 19 males in five generations with mild to borderline non-syndromic X-linked mental retardation (MRX). There were no clinical manifestations in the affected males other than mental impairment and relatively long ears, with neuropsychiatric problems in some cases. Linkage analysis carried out on part of the pedigree using 34 markers spanning the X chromosome localized the gene between DXS454 and DXS1001 in Xq23. The maximum two-point lod score was 3.21 at DXS1059. PAK3 is a known MRX gene mapping to the same region. The affected males and obligate carrier females were found to have a missense mutation c. 1094C > A in exon 10 causing an A365E substitution in a highly conserved region of the protein. The C to A base change abolishes a PvuII restriction enzyme site providing the basis for a simple test, if required, for carrier detection and prenatal diagnosis in the extended family. (C) 2003 Wiley-Liss, Inc.