Recessive mutations in >VPS13D cause childhood onset movement disorders
Recessive mutations in >VPS13D cause childhood onset movement disorders
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DOI：
10.1002/ana.25204
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发表时间：
2018-06-01
影响因子：
11.2
通讯作者：
Campeau, Philippe M.
中科院分区：
文献类型：
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作者：
Gauthier, Julie;Meijer, Inge A.;Campeau, Philippe M.
VPS13蛋白家族成员VPS13A到VPS13C与多种隐性运动障碍相关。我们描述了罕见的隐性VPS13D变异的第一种疾病关联，包括移码、错义和部分重复突变与一种新的复杂的多动神经障碍。临床特征包括发育迟缓，儿童期起病的运动障碍(舞蹈症、肌张力障碍或震颤)，以及进行性痉挛性共济失调或瘫痪。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综合征和编织棘细胞增多症。1例肌肉活检发现线粒体聚集和脂肪沉积，提示线粒体功能障碍。这些发现强调了VPS13复合体在神经系统疾病中的重要性以及在线粒体功能中的可能作用。Ann Neurol 2018；83：1089-1095
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