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Rare variants in IMPDH2 cause autosomal dominant dystonia in Chinese population

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Abstract

Study objectives

Recently, IMPDH2 has been linked to dystonia. However, no replication study from other cohorts has been conducted to confirm the association. We aimed to systematically evaluate the genetic associations of IMPDH2 with dystonia in a large dystonia cohort.

Methods

We analyzed rare variants (minor allele frequency < 0.01) of IMPDH2 in 688 Chinese dystonia patients with whole exome sequencing. The over-representation of rare variants in patients was examined with Fisher’s exact test at allele and gene levels.

Results

Four rare variants were detected in IMPDH2 in four patients with dystonia in our cohort, including three missense variants (p.Ser508Leu, p.Ala396Thr, and p.Phe24Val) and one splice acceptor variant (c.1296-1G>T). Two of them (c.1296-1G>T and p.Ser508Leu) were co-segregated in the family co-segregation analysis and were classified as pathogenic and likely pathogenic variant according to the American College of Medical Genetics and Genomics (ACMG) guidelines, respectively. Gene burden analysis revealed enrichment of rare variants in IMPDH2 in dystonia.

Conclusions

Our work supplemented the evidence on the role of IMPDH2 in autosomal dominant dystonia in Chinese population, and expanded the genetic and phenotypic spectrum of IMPDH2, paving way for future studies.

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Data availability

Anonymized data will be shared upon request with any qualified investigator.

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Acknowledgements

The authors would like to thank the patients and their families for their participation in the study.

Funding

This study was supported by the Sichuan Science and Technology Program (Grant No. 2022ZDZX0023).

Author information

Author notes

  1. Junyu Lin and Chunyu Li have contributed equally to the study.

Authors and Affiliations

  1. Department of Neurology, Rare Disease Center, Laboratory of Neurodegenerative Disorders, West China Hospital, Sichuan University, No 37, Guo Xue Road, Chengdu, 610041, Sichuan, China

    Junyu Lin, Chunyu Li, Yiyuan Cui, Yanbing Hou, Lingyu Zhang, Ruwei Ou, Qianqian Wei, Kuncheng Liu, Tianmi Yang, Yi Xiao, Qirui Jiang, Bi Zhao, Jing Yang, Xueping Chen & Huifang Shang

Authors
  1. Junyu Lin
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  2. Chunyu Li
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Contributions

JL: (1) research project: a. conception, b. organization, c. execution; (2) statistical analysis: design; (3) manuscript: writing of the draft. CL: (1) Research project: A. conception, b. organization, c. execution; (2) statistical analysis: execution; (3) manuscript: revision of the draft. YC: Blood sample collection and DNA extraction. YH, LZ, RO, QW, KL, TY, YX, QJ, BZ, JY, and XC: patients’ enrollment. HS: (1) research project: a. conception; (2) statistical analysis: review and critique; (3) manuscript: revision of the draft.

Corresponding author

Correspondence to Huifang Shang.

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Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical standards

All procedures performed in this study were in accordance with the Ethics Committee of West China Hospital of Sichuan University. Written informed consent was obtained from all recruited participants.

Ethics approval

All procedures performed in this study were in accordance with the Ethics Committee of West China Hospital of Sichuan University.

Consent to participate

Written informed consent was obtained from all recruited participants.

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Lin, J., Li, C., Cui, Y. et al. Rare variants in IMPDH2 cause autosomal dominant dystonia in Chinese population. J Neurol 270, 2197–2203 (2023). https://doi.org/10.1007/s00415-023-11564-x

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  • DOI: https://doi.org/10.1007/s00415-023-11564-x

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