Molecular Diagnostic Laboratory and Division of Medical Genetics, Department of Pediatrics, Saint Justine University Hospital Center, Montreal, Canada.
Department of Neuroscience, University of Montreal, Montreal, Canada.
Ann Neurol. 2018 Jun;83(6):1089-1095. doi: 10.1002/ana.25204. Epub 2018 Apr 10.
VPS13 protein family members VPS13A through VPS13C have been associated with various recessive movement disorders. We describe the first disease association of rare recessive VPS13D variants including frameshift, missense, and partial duplication mutations with a novel complex, hyperkinetic neurological disorder. The clinical features include developmental delay, a childhood onset movement disorder (chorea, dystonia, or tremor), and progressive spastic ataxia or paraparesis. Characteristic brain magnetic resonance imaging shows basal ganglia or diffuse white matter T2 hyperintensities as seen in Leigh syndrome and choreoacanthocytosis. Muscle biopsy in 1 case showed mitochondrial aggregates and lipidosis, suggesting mitochondrial dysfunction. These findings underline the importance of the VPS13 complex in neurological diseases and a possible role in mitochondrial function. Ann Neurol 2018;83:1089-1095.
VPS13 蛋白家族成员 VPS13A 至 VPS13C 与各种隐性运动障碍有关。我们描述了第一个与罕见隐性 VPS13D 变体相关的疾病关联，包括移码、错义和部分重复突变，以及一种新的复杂的、多动性的神经障碍。临床特征包括发育迟缓、儿童期发病的运动障碍（舞蹈症、肌张力障碍或震颤），以及进行性痉挛性共济失调或截瘫。特征性的脑磁共振成像显示基底节或弥漫性白质 T2 高信号，如 Leigh 综合征和舞蹈棘红细胞增多症所见。1 例肌肉活检显示线粒体聚集和脂肪变性，提示线粒体功能障碍。这些发现强调了 VPS13 复合物在神经疾病中的重要性，以及在线粒体功能中的可能作用。《神经病学年鉴》2018 年；83:1089-1095。
