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 &g...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-01-01
|
| Series: | npj Genomic Medicine |
| Online Access: | https://doi.org/10.1038/s41525-020-00165-6 |
| _version_ | 1818754001117642752 |
|---|---|
| author | Hai-Lin Dong Jia-Qi Li Gong-Lu Liu Hao Yu Zhi-Ying Wu |
| author_facet | Hai-Lin Dong Jia-Qi Li Gong-Lu Liu Hao Yu Zhi-Ying Wu |
| author_sort | Hai-Lin Dong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T05:16:18Z |
| format | Article |
| id | doaj.art-16f9d9bdfe284a10959058de45bf4c41 |
| institution | Directory Open Access Journal |
| issn | 2056-7944 |
| language | English |
| last_indexed | 2024-12-18T05:16:18Z |
| publishDate | 2021-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Genomic Medicine |
| spelling | doaj.art-16f9d9bdfe284a10959058de45bf4c412022-12-21T21:19:46ZengNature Portfolionpj Genomic Medicine2056-79442021-01-01611510.1038/s41525-020-00165-6Biallelic SORD pathogenic variants cause Chinese patients with distal hereditary motor neuropathyHai-Lin Dong0Jia-Qi Li1Gong-Lu Liu2Hao Yu3Zhi-Ying Wu4Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of MedicineDepartment of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of MedicineDepartment of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of MedicineDepartment of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of MedicineDepartment of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of MedicineAbstract 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.https://doi.org/10.1038/s41525-020-00165-6 |
| spellingShingle | Hai-Lin Dong Jia-Qi Li Gong-Lu Liu Hao Yu Zhi-Ying Wu Biallelic SORD pathogenic variants cause Chinese patients with distal hereditary motor neuropathy npj Genomic Medicine |
| title | Biallelic SORD pathogenic variants cause Chinese patients with distal hereditary motor neuropathy |
| title_full | Biallelic SORD pathogenic variants cause Chinese patients with distal hereditary motor neuropathy |
| title_fullStr | Biallelic SORD pathogenic variants cause Chinese patients with distal hereditary motor neuropathy |
| title_full_unstemmed | Biallelic SORD pathogenic variants cause Chinese patients with distal hereditary motor neuropathy |
| title_short | Biallelic SORD pathogenic variants cause Chinese patients with distal hereditary motor neuropathy |
| title_sort | biallelic sord pathogenic variants cause chinese patients with distal hereditary motor neuropathy |
| url | https://doi.org/10.1038/s41525-020-00165-6 |
| work_keys_str_mv | AT hailindong biallelicsordpathogenicvariantscausechinesepatientswithdistalhereditarymotorneuropathy AT jiaqili biallelicsordpathogenicvariantscausechinesepatientswithdistalhereditarymotorneuropathy AT gongluliu biallelicsordpathogenicvariantscausechinesepatientswithdistalhereditarymotorneuropathy AT haoyu biallelicsordpathogenicvariantscausechinesepatientswithdistalhereditarymotorneuropathy AT zhiyingwu biallelicsordpathogenicvariantscausechinesepatientswithdistalhereditarymotorneuropathy |