Department of Neurology, University of Washington, 1660 S. Columbian way S127, Seattle WA, United States; Department of Neurology, VA Puget Sound Medical Center, United States.
Department of Neurology, University of Washington, 1660 S. Columbian way S127, Seattle WA, United States.
Neuromuscul Disord. 2020 Jul;30(7):572-575. doi: 10.1016/j.nmd.2020.05.005. Epub 2020 May 23.
Distal hereditary motor neuropathy (dHMN) is an inherited neuromuscular disease characterized by symmetric distal weakness and atrophy without sensory changes. There are about thirty known genes associated with dHMN, but together they explain only about a third of cases. Mutations in the sigma non-opioid intracellular receptor 1 gene (SIGMAR1) has been linked to autosomal recessive dHMN with pyramidal signs in several families. This phenotype can mimic amyotrophic lateral sclerosis (ALS). We report a 39-year-old man who was referred to our ALS clinic with distal motor weakness and hyperreflexia. Whole exome sequencing identified two novel variants in the SIGMAR1 gene in the proband. Targeted Sanger sequencing of asymptomatic family members confirmed that each carried one of these two variants. Our findings expand the number of known SIGMAR1 pathogenic variants associated with dHMN, which should be clinically distinguished from ALS.
遗传性远端运动神经病（dHMN）是一种以对称性远端无力和萎缩为特征的遗传性神经肌肉疾病，无感觉改变。约有三十个已知基因与 dHMN 相关，但它们共同仅能解释约三分之一的病例。在几个家族中，sigma 非阿片类细胞内受体 1 基因（SIGMAR1）的突变与常染色体隐性遗传的伴有锥体束征的 dHMN 有关。这种表型可模拟肌萎缩侧索硬化症（ALS）。我们报告了一名 39 岁的男性，因远端运动无力和反射亢进而被转诊至我们的 ALS 诊所。全外显子组测序在该先证者中发现了 SIGMAR1 基因中的两个新的变异。对无症状的家族成员进行靶向 Sanger 测序证实，每个人都携带这两个变异中的一个。我们的发现扩大了与 dHMN 相关的已知 SIGMAR1 致病性变异的数量，应与 ALS 进行临床鉴别。
