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Sub-region analysis of DMD gene in cases with idiopathic generalized epilepsy

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Abstract

Gene sub-region encoded protein domain is the basic unit for protein structure and function. The DMD gene is the largest coding gene in humans, with its phenotype relevant to idiopathic generalized epilepsy. We hypothesized variants clustered in sub-regions of idiopathic generalized epilepsy genes and investigated the relationship between the DMD gene and idiopathic generalized epilepsy. Whole exome sequencing was performed in 106 idiopathic generalized epilepsy individuals. DMD variants were filtered with variant type, allele frequency, in silico prediction, hemizygous or homozygous status in the population, inheritance mode, and domain location. Variants located at the sub-regions were selected by the subRVIS software. The pathogenicity of variants was evaluated by the American College of Medical Genetics and Genomics criteria. Articles on functional studies related to epilepsy for variants clustered protein domains were reviewed. In sub-regions of the DMD gene, two variants were identified in two unrelated cases with juvenile absence epilepsy or juvenile myoclonic epilepsy. The pathogenicity of both variants was uncertain significance. Allele frequency of both variants in probands with idiopathic generalized epilepsy reached statistical significance compared with the population (Fisher’s test, p = 2.02 × 10−6, adjusted α = 4.52 × 10−6). The variants clustered in the spectrin domain of dystrophin, which binds to glycoprotein complexes and indirectly affects ion channels contributing to epileptogenesis. Gene sub-region analysis suggests a weak association between the DMD gene and idiopathic generalized epilepsy. Functional analysis of gene sub-region helps infer the pathogenesis of idiopathic generalized epilepsy.

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Acknowledgements

We are grateful to subRVIS and Figdraw for providing Figs. 2 and 4. We thank the probands and their parents for participating in the study.

Funding

This study is funded by the Fujian Provincial Health Technology Project (grant number 2019-ZQN-94) and the Natural Science Foundation of Fujian Province (grant number 2020J011257). The funders had no role in study design, data collection, data analysis, data interpretation, and decision to prepare or publish the manuscript.

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  1. Zhi-Jian Lin and Bi-Xia Huang contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, The Affiliated Hospital of Putian University, Brain Science Institute of Putian University, 999 Dongzhen East Road, Licheng District, Putian, 351100, China

    Zhi-Jian Lin, Bi-Xia Huang, Li-Fang Su, Sheng-Yin Zhu, Jun-Wei He, Guo-Zhang Chen & Peng-Xing Lin

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  1. Zhi-Jian Lin
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Contributions

Zhi-Jian Lin contributed to the conception and design of the study. Zhi-Jian Lin and Bi-Xia Huang performed material preparation, data collection, and analysis. Zhi-Jian Lin wrote the first draft of the manuscript, and all authors commented on previous versions. All authors read and approved the final manuscript.

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Correspondence to Peng-Xing Lin.

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Highlights

• Gene sub-region analysis in individuals with idiopathic generalized epilepsy.

• Variants clustered in spectrin in the idiopathic generalized epilepsy cases.

• Spectrin indirectly affects ion channels contributing to epileptogenesis.

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Lin, ZJ., Huang, BX., Su, LF. et al. Sub-region analysis of DMD gene in cases with idiopathic generalized epilepsy. Neurogenetics 24, 161–169 (2023). https://doi.org/10.1007/s10048-023-00715-x

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  • DOI: https://doi.org/10.1007/s10048-023-00715-x

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