Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
Am J Med Genet A. 2011 Sep;155A(9):2071-7. doi: 10.1002/ajmg.a.34165. Epub 2011 Aug 10.
Polymicrogyria is a disorder of neuronal development resulting in structurally abnormal cerebral hemispheres characterized by over-folding and abnormal lamination of the cerebral cortex. Polymicrogyria is frequently associated with severe neurologic deficits including intellectual disability, motor problems, and epilepsy. There are acquired and genetic causes of polymicrogyria, but most patients with a presumed genetic etiology lack a specific diagnosis. Here we report using whole-exome sequencing to identify compound heterozygous mutations in the WD repeat domain 62 (WDR62) gene as the cause of recurrent polymicrogyria in a sibling pair. Sanger sequencing confirmed that the siblings both inherited 1-bp (maternal allele) and 2-bp (paternal allele) frameshift deletions, which predict premature truncation of WDR62, a protein that has a role in early cortical development. The probands are from a non-consanguineous family of Northern European descent, suggesting that autosomal recessive PMG due to compound heterozygous mutation of WDR62 might be a relatively common cause of PMG in the population. Further studies to identify mutation frequency in the population are needed.
脑回小畸形是一种神经元发育紊乱，导致大脑半球结构异常，表现为大脑皮层过度折叠和异常分层。脑回小畸形常伴有严重的神经功能缺陷，包括智力障碍、运动问题和癫痫。脑回小畸形有获得性和遗传性病因，但大多数具有遗传病因假定的患者缺乏明确的诊断。本研究报告了使用全外显子组测序鉴定 WD 重复结构域 62（WDR62）基因的复合杂合突变，是一对同胞反复发生脑回小畸形的原因。Sanger 测序证实，这对同胞均遗传了 1 个碱基（母本等位基因）和 2 个碱基（父本等位基因）的移码缺失，预测 WDR62 蛋白的提前截断，该蛋白在早期皮质发育中起作用。先证者来自北欧非近亲家族，提示由于 WDR62 复合杂合突变导致的常染色体隐性遗传 PMG 可能是人群中 PMG 的一个相对常见的原因。需要进一步研究以确定人群中的突变频率。
