Genetic Diagnosis Spectrum and Multigenic Burden of Exome-Level Rare Variants in a Childhood Epilepsy Cohort

Yao, Ruen and Zhou, Yunqing and Tang, Jie and Li, Niu and Yu, Tingting and He, Yingzhong and Wang, Cuijin and Wang, Jiwen and Wang, Jian (2021) Genetic Diagnosis Spectrum and Multigenic Burden of Exome-Level Rare Variants in a Childhood Epilepsy Cohort. Frontiers in Genetics, 12. ISSN 1664-8021

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Abstract

Childhood epilepsy is a considerably heterogeneous neurological condition with a high worldwide incidence. Genetic diagnosis of childhood epilepsy provides the most accurate pathogenetic evidence; however, a large proportion of highly suspected cases remain undiagnosed. Accumulation of rare variants at the exome level as a multigenic burden contributing to childhood epilepsy should be further evaluated. In this retrospective analysis, exome-level sequencing was used to depict the mutation spectra of 294 childhood epilepsy patients from Shanghai Children’s Medical Center, Department of Neurology. Furthermore, variant information from exome sequencing data was analyzed apart from monogenic diagnostic purposes to elucidate the possible multigenic burden of rare variants related to epilepsy pathogenesis. Exome sequencing reached a diagnostic rate of 30.61% and identified six genes not currently listed in the epilepsy-associated gene list. A multigenic burden study revealed a three-fold possibility that deleterious missense mutations in ion channel and synaptic genes in the undiagnosed cohort may contribute to the genetic risk of childhood epilepsy, whereas variants in the gene categories of cell growth, metabolic, and regulatory function showed no significant difference. Our study provides a comprehensive overview of the genetic diagnosis of a Chinese childhood epilepsy cohort and provides novel insights into the genetic background of these patients. Harmful missense mutations in genes related to ion channels and synapses are most likely to produce a multigenic burden in childhood epilepsy.

Item Type: Article
Subjects: Open Library Press > Medical Science
Depositing User: Unnamed user with email support@openlibrarypress.com
Date Deposited: 04 Jan 2023 07:27
Last Modified: 04 Jan 2023 07:27
URI: https://openlibrarypress.com/id/eprint/45

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