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

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.

SUBMITTER: Dong HL

PROVIDER: S-EPMC7782788 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Dong Hai-Lin HL Li Jia-Qi JQ Liu Gong-Lu GL Yu Hao H Wu Zhi-Ying ZY

NPJ genomic medicine 20210104 1

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 tran ...[more]

PMID: 33397963

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