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

被引：18

作者：

Dong, Hai-Lin ^{[1
,2
,3
]}

Li, Jia-Qi ^{[1
,2
,3
]}

Liu, Gong-Lu ^{[1
,2
,3
,4
,5
]}

Yu, Hao ^{[1
,2
,3
]}

Wu, Zhi-Ying ^{[1
,2
,3
]}

机构：

[1] Zhejiang Univ, Sch Med, Dept Neurol, Hangzhou, Peoples R China

[2] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Res Ctr Neurol, Hangzhou, Peoples R China

[3] Zhejiang Univ, Sch Med, Key Lab Med Neurobiol Zhejiang Prov, Hangzhou, Peoples R China

[4] Fudan Univ, Huashan Hosp, Shanghai Med Coll, Dept Neurol, Shanghai, Peoples R China

[5] Fudan Univ, Huashan Hosp, Shanghai Med Coll, Inst Neurol, Shanghai, Peoples R China

来源：

NPJ GENOMIC MEDICINE | 2021年 / 6卷 / 01期

关键词：

PREDICTION; MUTATIONS;

D O I：

10.1038/s41525-020-00165-6

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：5

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