Mapping of MRX81 in Xp11.2-Xq12 suggests the presence of a new gene involved in nonspecific X-linked mental retardation
Mapping of MRX81 in Xp11.2-Xq12 suggests the presence of a new gene involved in nonspecific X-linked mental retardation
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DOI：
10.1002/ajmg.a.10144
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发表时间：
2003-04-30
影响因子：
2
通讯作者：
Miano, MG
中科院分区：
文献类型：
--
作者：
Annunziata, I;Lanzara, C;Miano, MG
X连锁非特异性精神发育迟滞（MRX）约占男性精神发育迟滞的25%。许多MRX基因座已被定位在X染色体上，反映了中枢神经系统（CNS）规格和功能中基因作用的复杂性。已经鉴定了11个MRX基因，但许多其他致病基因座仍有待细化到单基因水平。在21个MRX家族中，致病基因位于近着丝粒区域;我们在这里报告通过连锁分析鉴定了另一个这样的位点，MRX 81。新的MRX基因座是通过对一个意大利大家庭进行的两点和多点参数分析确定的。观察到MRX 81与DNA标记物ALAS 2、DXS 991和DXS 7132紧密连锁，最大LOD评分为3.43。单倍型构建描绘了DXS 1039和DXS 1216之间8 cM的MRX 81关键区域，这是迄今为止描述的最小MRX着丝粒周围间隔，并将其置于Xp11.2-Xq 12中。到目前为止，对该区域的两个候选基因，MRX基因寡聚蛋白（OPHN 1）和脑特异性ephrinB 1（EFNB 1）基因进行自动测序，从受影响的男性DNA中排除了它们对MRX 81的候选资格，这表明了一种新的疾病基因。(C)2003 Wiley-Liss，Inc.
X-linked nonspecific mental retardation (MRX) accounts for similar to25% of mental retardation in males. A number of MRX loci have been mapped on the X chromosome, reflecting the complexity of gene action in central nervous system (CNS) specification and function. Eleven MRX genes have been identified, but many other causative loci remain to be refined to the single gene level. In 21 MRX families, the causative gene is located in the pericentromeric region; and we report here the identification by linkage analysis of a further such locus, MRX81. The new MRX locus was identified by two- and multi-point parametric analysis carried out on a large Italian family. Tight linkage of MRX81 to DNA markers ALAS2, DXS991, and DXS7132 was observed with a maximum LOD score of 3.43. Haplotype construction delineates an MRX81 critical region of 8 cM, the smallest MRX pericentromeric interval so far described, between DXS1039 and DXS1216, and placing it in Xp11.2-Xq12. So far, automated sequencing of two candidates in the region, the MRX gene oligophrenin (OPHN1) and the brain-specific ephrinB1 (EFNB1) gene, in DNA from affected males excluded their candidacy for MRX81, suggesting a novel disease gene. (C) 2003 Wiley-Liss, Inc.