PDF(Pubmed)
Abstract：
Bilateral perisylvian polymicrogyria is the most common form of regional polymicrogyria within malformations of cortical development, constituting 20% of all malformations of cortical development. Bilateral perisylvian polymicrogyria is characterized by an excessive folding of the cerebral cortex and abnormal cortical layering. Notable clinical features include upper motoneuron dysfunction, dysarthria and asymmetric quadriparesis. Cognitive impairment and epilepsy are frequently observed. To identify genetic variants underlying bilateral perisylvian polymicrogyria in Finland, we examined 21 families using standard exome sequencing, complemented by optical genome mapping and/or deep exome sequencing. Pathogenic or likely pathogenic variants were identified in 5/21 (24%) of families, of which all were confirmed as de novo. These variants were identified in five genes, i.e. DDX23, NUS1, SCN3A, TUBA1A and TUBB2B, with NUS1 and DDX23 being associated with bilateral perisylvian polymicrogyria for the first time. In conclusion, our results confirm the previously reported genetic heterogeneity of bilateral perisylvian polymicrogyria and underscore the necessity of more advanced methods to elucidate the genetic background of bilateral perisylvian polymicrogyria.
摘要：
在皮质发育的畸形中，双侧包膜多囊是最常见的区域性多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多囊多占皮质发育所有畸形的20%。双侧包膜polymicrogyria的特征是大脑皮层过度折叠和皮质分层异常。值得注意的临床特征包括上运动神经元功能障碍，构音障碍和不对称四肢轻瘫。经常观察到认知障碍和癫痫。为了确定芬兰双侧PerisylvianPolymicrogyria的遗传变异，我们使用标准外显子组测序检查了21个家族，辅以光学基因组作图和/或深度外显子组测序。在5/21（24％）的家庭中发现了致病性或可能的致病性变异，其中全部被确认为从头。这些变异在五个基因中被鉴定出来,即DDX23、NUS1、SCN3A、TUBA1A和TUBB2B，NUS1和DDX23首次与双侧包膜polymicrogyria相关。总之,我们的研究结果证实了先前报道的双侧perisylviapolymicrogyria的遗传异质性，并强调了需要更先进的方法来阐明双侧perisylviapolymicrogyria的遗传背景。
