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Whole exome sequencing reveals a broader variant spectrum of Charcot-Marie-Tooth disease type 2

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Abstract

Charcot-Marie-Tooth disease type 2 (CMT2) is a clinically and genetically heterogeneous inherited neuropathy. Although new causative and disease-associated genes have been identified for CMT2 in recent years, molecular diagnoses are still lacking for a majority of patients. We here studied a cohort of 35 CMT2 patients of Chinese descent, using whole exome sequencing to investigate gene mutations and then explored relationships among genotypes, clinical features, and mitochondrial DNA levels in blood as assessed by droplet digital PCR. We identified pathogenic variants in 57% of CMT2 patients. The most common genetic causes in the cohort were MFN2 mutations. Two patients with typical CMT phenotype and neuromyotonia were detected to harbor compound heterozygous variations in the HINT1 gene. In conclusion, our work supports that the molecular diagnostic rate of CMT2 patients can be increased via whole exome sequencing, and our data suggest that assessment of possible HINT1 mutations should be undertaken for CMT2 patients with neuromyotonia.

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Acknowledgments

We would like to thank all the participants for their help and willingness to participate in this study. We thank the reviewers for the comments. This work was supported by the grant 81500980 and U1505222 from the National Natural Science Foundation of China, grant 81870929 from the National Natural Science Foundation of China, and grant 2018-CX-25 from Medical Innovation Project for Research Talents of Fujian Province.

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  1. Shan Lin and Liu-Qing Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology and Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China

    Shan Lin, Liu-Qing Xu, Guo-Rong Xu, Ling-Ling Guo, Bi-Juan Lin, Wan-Jin Chen, Ning Wang, Yi Lin & Jin He

  2. Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, 350005, China

    Shan Lin, Wan-Jin Chen, Ning Wang, Yi Lin & Jin He

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  1. Shan Lin
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Contributions

Study concept and design (Jin He and Yi Lin); acquisition of data (Jin He, Shan Lin, Liuqing Xu, Guorong Xu, Ling-Ling Guo); analysis and interpretation of data (Jin He, Shan Lin, Liuqing Xu, Ling-Ling Guo); drafting of the manuscript (Jin He, Shan Lin, Bi-Juan Lin); critical revision of the manuscript for important intellectual content (Jin He and Yi Lin); obtaining of funding (Jin He and Yi Lin); study supervision (Ning Wang and Wanjin Chen).

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Correspondence to Yi Lin or Jin He.

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Written informed consent was obtained from all the patients included in this study. This study was approved by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University.

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Lin, S., Xu, LQ., Xu, GR. et al. Whole exome sequencing reveals a broader variant spectrum of Charcot-Marie-Tooth disease type 2. Neurogenetics 21, 79–86 (2020). https://doi.org/10.1007/s10048-019-00591-4

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