Genotype-phenotype analysis of human frontoparietal polymicrogyria syndromes
Genotype-phenotype analysis of human frontoparietal polymicrogyria syndromes
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DOI：
10.1002/ana.20616
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发表时间：
2005-11-01
影响因子：
11.2
通讯作者：
Walsh, CA
中科院分区：
文献类型：
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作者：
Piao, XH;Chang, BS;Walsh, CA
人类大脑皮质多微回症是一种异质性疾病，只有一个已知的基因（GPR56）与一个明显独特的表型，称为双侧额顶多微回症（BFPP）。为了确定可能由人类GPR56突变引起的异常范围并建立BFPP的诊断标准，我们分析了29例典型BFPP患者的GPR56基因。我们在所有29例典型BFPP患者中鉴定了纯合GPR56突变。所发现的总共11GPR56突变代表了全世界各种群体中的各种不同的创始者突变。此外，我们分析了5例未显示GPR56突变的BFPP患者，发现他们定义了一种临床、影像学和遗传学上不同的综合征，我们称之为BFPP2。最后，我们研究了7例患有其他多种多微脑回综合征的患者，包括双侧额叶多微脑回，双侧大脑外侧裂周围多微脑回和双侧全身性多微脑回。在这些患者中未发现GPR56突变。本研究提供了BFPP表型的分子确认，并提供了必要的诊断筛选。
Human cerebral cortical polymicrogyria is a heterogeneous disorder, with only one known gene (GPR56) associated with an apparently distinctive phenotype, termed bilateral frontoparietal polymicrogyria (BFPP). To define the range of abnormalities that could be caused by human GPR56 mutations and to establish diagnostic criteria for BFPP, we analyzed the GPR56 gene in a cohort of 29 patients with typical BFPP. We identified homozygous GPR56 mutations in all 29 patients with typical BFPP. The total of I I GPR56 mutations found represented a variety of distinct founder mutations in various populations throughout the world. In addition, we analyzed five patients with BFPP who did not show GPR56 mutation and found that they define a clinically, radiographically, and genetically distinct syndrome that we termed BFPP2. Finally, we studied seven patients with a variety of other polymicrogyria syndromes including bilateral frontal polymicrogyria, bilateral perisylvian polymicrogyria, and bilateral generalized polymicrogyria. No GPR56 mutation was found in these patients. This study provides a molecular confirmation of the BFPP phenotype and provides the wherewithal for diagnostic screening.