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A novel Q93H missense mutation in DCTN1 caused distal hereditary motor neuropathy type 7B and Perry syndrome from a Chinese family

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Abstract

The Dynactin 1 (DCTN1) encodes the p150 subunit of dynactin, which engages retrograde axonal transport. Missense mutations in DCTN1 have been linked to a series of neurodegenerative diseases, including distal hereditary motor neuropathies (dHMN) and Perry syndrome. A few pathogenic DCTN1 mutations related with Perry syndrome have been described within, or adjacent to, the highly conserved N-terminal cytoskeleton-associated protein, glycine-rich (CAP-Gly) domain. But to our best knowledge, only the pathogenic G59S mutation in DCTN1 has been reported in dHMN7B families. Herein, we provided a novel heterozygous mutation in DCTN1 which caused both dHMN7B and Perry syndrome from a Chinese family. Whole exome sequencing (WES) was performed to identify the disease-associated genes. Single nucleotide variants (SNVs) and small insertions/deletions (INDELs) were further predicted with Mutation Taster, Polymorphism Phenoty** v2 (PolyPhen-2), and Sorting Intolerant From Tolerant (SIFT) and compared to the Single Nucleotide Polymorphism Database(dbSNP), Exome Aggregation Consortium (ExAC), and the 1000 Genomes Project. Furthermore, a novel missense mutation c.279G>C (Q93H) in DCTN1 was identified as the candidate loci. The mutation was confirmed with Sanger sequencing in the family members and cosegregated with various phenotypes. In silico analysis and molecular structural modeling, the mutation not only caused the loss of a hydrogen bond within the p150 protein but also affected the formation of hydrogen bonds between p150 and EB. Therefore, the new Q93H mutation in DCTN1 caused both familial dHMN7B and Perry syndrome. Our findings could expand the clinical and pathogenic spectrum and strengthen the clinical diagnostic role of the DCTN1 gene.

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Author notes

  1. **gfei Zhang and Hong Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, First Hospital, Shanxi Medical University, No.85, Jiefang South Street, Taiyuan, China

    **gfei Zhang, Hong Wang, Juan Wang, **g Zhang, Xueli Chang, Shan Huang, **aomin Pang, Junhong Guo, Qiuhong Wang & Wei Zhang

  2. School of Mathematics and Statistics, Shandong University, Shandong, China

    Wenjie Liu

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  1. **gfei Zhang
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  2. Hong Wang
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  4. Juan Wang
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Correspondence to Wei Zhang.

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All procedures were approved by the Ethics committee of First Hospital of Shanxi Medical University (Taiyuan, China) and carried out in accordance with the principles of Helsinki Declaration.

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Zhang, J., Wang, H., Liu, W. et al. A novel Q93H missense mutation in DCTN1 caused distal hereditary motor neuropathy type 7B and Perry syndrome from a Chinese family. Neurol Sci 42, 3695–3705 (2021). https://doi.org/10.1007/s10072-020-04962-w

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