An autosomal recessive form of bilateral frontoparietal polymicrogyria maps to chromosome 16q12.2-21
An autosomal recessive form of bilateral frontoparietal polymicrogyria maps to chromosome 16q12.2-21
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DOI：
10.1086/339552
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发表时间：
2002-04-01
影响因子：
9.8
通讯作者：
Walsh, CA
中科院分区：
文献类型：
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作者：
Piao, XH;Basel-Vanagaite, L;Walsh, CA
多小脑回畸形是一种大脑皮质畸形，大体上表现为皮质过度折叠，显微镜下表现为皮质分层异常。尽管多小脑回畸形似乎有一个或多个遗传原因，但尚未确定多小脑回畸形的基因位点。在此我们描述了一种新的多小脑回畸形遗传形式的临床和影像学特征，并定位了相关基因。我们利用连锁分析研究了两个近亲的巴勒斯坦家系，其患有常染色体隐性遗传形式的双侧额顶叶多小脑回畸形（BFPP）。五名患病儿童有中重度智力障碍、发育迟缓以及内斜视，五名患病儿童中有四名出现癫痫发作。脑部磁共振成像显示多小脑回畸形在额叶和顶叶最为显著，但也涉及其他皮质区域。一项全基因组连锁筛查揭示了一个在两个家系的患病儿童中由遗传获得相同的单一基因位点，并显示出一种单一的疾病相关单倍型，提示存在一个共同的始祖突变。BFPP的基因位点定位于16号染色体16q12.2 - 21，最小区间为17厘摩。对于D16S514，最大合并两点对数优势计分（LOD score）为3.98，最大多点LOD score为4.57。这项研究提供了首个遗传学证据，表明BFPP是一种常染色体隐性遗传病，并为确定相关基因提供了一个起点。
Polymicrogyria is a cerebral cortical malformation that is grossly characterized by excessive cortical folding and microscopically characterized by abnormal cortical layering. Although polymicrogyria appears to have one or more genetic causes, no polymicrogyria loci have been identified. Here we describe the clinical and radiographic features of a new genetic form of polymicrogyria and localize the responsible gene. We studied two consanguineous Palestinian pedigrees with an autosomal recessive form of bilateral frontoparietal polymicrogyria (BFPP), using linkage analysis. Five affected children had moderate-to-severe mental retardation, developmental delay, and esotropia, and four of the five affected children developed seizures. Brain magnetic-resonance imaging revealed polymicrogyria that was most prominent in the frontal and parietal lobes but involved other cortical areas as well. A genomewide linkage screen revealed a single locus that was identical by descent in affected children in both families and showed a single disease-associated haplotype, suggesting a common founder mutation. The locus for BFPP maps to chromosome 16q12.2-21, with a minimal interval of 17 cM. For D16S514, the maximal pooled two-point LOD score was 3.98, and the maximal multipoint LOD score was 4.57. This study provides the first genetic evidence that BFPP is an autosomal recessive disorder and serves as a starting point for the identification of the responsible gene.