De Novo DNM1L Variant in a Teenager With Progressive Paroxysmal Dystonia and Lethal Super-refractory Myoclonic Status Epilepticus.
De Novo DNM1L Variant in a Teenager With Progressive Paroxysmal Dystonia and Lethal Super-refractory Myoclonic Status Epilepticus.
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DOI：
10.1177/0883073818778203
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发表时间：
2018-09
影响因子：
1.9
通讯作者：
Payne ET
中科院分区：
文献类型：
--
作者：
Ryan CS;Fine AL;Cohen AL;Schiltz BM;Renaud DL;Wirrell EC;Patterson MC;Boczek NJ;Liu R;Babovic-Vuksanovic D;Chan DC;Payne ET
动力蛋白1类基因(DNM1L)编码一种GTP酶，介导线粒体和过氧化物体的分裂和融合。我们报告了一个与DNM1L致病变异相关的新的临床表现，并回顾了文献。一名13岁男孩，轻度发育迟缓和阵发性肌张力障碍，急性表现为多灶性肌阵挛超难治性癫痫持续状态。尽管进行了持续和积极的治疗，但癫痫仍在继续，在全球皮质广泛萎缩的情况下，最终取消了护理。快速三外显子全外显子测序发现DNM1L存在一个新生杂合子c.1207C>；T(p.R403C)致病变异体。成纤维细胞线粒体免疫荧光染色显示异常拉长和管状形态。此病例强调了在重症监护环境中快速进行整个外显子组测序的诊断重要性，并揭示了与DNM1L变异相关的不断扩大的表型谱。这现在包括进行性阵发性肌张力障碍和青春期发作的超顽固性肌阵挛持续状态癫痫，导致惊人的快速和进行性皮质萎缩和死亡。
The dynamin 1-like gene (DNM1L) encodes a GTPase that mediates mitochondrial and peroxisomal fission and fusion. We report a new clinical presentation associated with a DNM1L pathogenic variant and review the literature. A 13-year-old boy with mild developmental delays and paroxysmal dystonia presented acutely with multifocal myoclonic super-refractory status epilepticus. Despite sustained and aggressive treatment, seizures persisted and care was ultimately withdrawn in the context of extensive global cortical atrophy. Rapid trio-whole exome sequencing revealed a de novo heterozygous c.1207C>T (p.R403C) pathogenic variant in DNM1L. Immunofluorescence staining of fibroblast mitochondria revealed abnormally elongated and tubular morphology. This case highlights the diagnostic importance of rapid whole exome sequencing within a critical care setting and reveals the expanding phenotypic spectrum associated with DNM1L variants. This now includes progressive paroxysmal dystonia and adolescent-onset super-refractory myoclonic status epilepticus contributing to strikingly rapid and progressive cortical atrophy and death.
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