Biallelic SORD pathogenic variants cause Chinese patients with distal hereditary motor neuropathy

Hai-Lin Dong; Jia-Qi Li; Gong-Lu Liu; Hao Yu; Zhi-Ying Wu

doi:10.1038/s41525-020-00165-6

Biallelic SORD pathogenic variants cause Chinese patients with distal hereditary motor neuropathy

NPJ Genom Med. 2021 Jan 4;6(1):1. doi: 10.1038/s41525-020-00165-6.

Authors

Hai-Lin Dong¹, Jia-Qi Li¹, Gong-Lu Liu^{1

2}, Hao Yu¹, Zhi-Ying Wu³

Affiliations

¹ Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.
² Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
³ Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China. zhiyingwu@zju.edu.cn.

Abstract

Sorbitol dehydrogenase gene (SORD) has been identified as a novel causative gene of recessive forms of hereditary neuropathy, including Charcot-Marie-Tooth disease type 2 and distal hereditary motor neuropathy (dHMN). Our findings reveal two novel variants (c.404 A > G and c.908 + 1 G > C) and one known variant (c.757delG) within SORD in four Chinese dHMN families. Ex vivo cDNA polymerase chain reaction confirmed that c.908 + 1 G > C variant was associated with impaired splicing of the SORD transcript. In vitro cell functional studies showed that c.404 A > G variant resulted in aggregate formation of SORD and low protein solubility, confirming the pathogenicity of SORD variants. We have provided more evidence to establish SORD as a causative gene for dHMN.