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CASE REPORT article

Front. Genet.

Sec. Genetics of Common and Rare Diseases

Volume 16 - 2025 | doi: 10.3389/fgene.2025.1477518

A novel SIGMAR1 missense mutation leads to distal hereditary motor neuropathy phenotype mimicking juvenile ALS: a case report of China

Provisionally accepted
Junhui Wang Junhui Wang 1Qinglong Yu Qinglong Yu 2Risna Begam Mohammed Nazar Risna Begam Mohammed Nazar 3Sihui chen Sihui chen 3Qiaoling Qian Qiaoling Qian 2Xueping Chen Xueping Chen 3*
  • 1 Mount Sinai Hospital, University of Toronto, Toronto, Canada
  • 2 Department of Neurology, Affiliated Hospital of Panzhihua University,Panzihua, China, panzhihua, China
  • 3 Department of Neurology, West China Hospital of Sichuan University, Chengdu, Sichuan, China

The final, formatted version of the article will be published soon.

    We present the case of a 16-year-old East Asian Chinese girl with a novel mutation in the SIGMAR1 gene, initially diagnosed as juvenile amyotrophic lateral sclerosis (JALS). At the age of five, she began to exhibit gait abnormalities while walking, a condition that persisted for four years until muscle weakness and atrophy emerged, predominantly affecting her distal muscles symmetrically. Electromyography (EMG) initially revealed early abonormal motor conduction, and subsequent examinations indicated neurogenic damage accompanied by localized denervation potentials. Whole-exome sequencing identified compound heterozygous mutations in the SIGMAR1 gene. Throughout the course of her illness, the patient exhibited slow disease progression without cognitive impairment or scoliosis development. We ultimately revised the diagnosis to distal hereditary motor neuropathy (dHMN). This study reports the case of SIGMAR1 new locus mutation leading to dHMN in China, contributing to the expansion of the dHMN genetic database. In our patient, the initial EMG findings indicated issues with neurogenic conduction, followed by a slow progression of the disease. Subsequently, EMG results revealed axonal damage and denervation potentials. These clinical features can easily lead to confusion with JALS. This insight is valuable for improving diagnostic accuracy and understanding the clinical spectrum of dHMN related to SIGMAR1 mutations.

    Keywords: SIGMAR, JALS, dHMN, diagnosis, case report

    Received: 14 Aug 2024; Accepted: 31 Mar 2025.

    Copyright: © 2025 Wang, Yu, Mohammed Nazar, chen, Qian and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xueping Chen, Department of Neurology, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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