Whole-exome sequencing of a large Japanese family with febrile seizures

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K10079
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Ibaraki Prefectural University of Health Science
• Principal Investigator: Nakayama Junko 茨城県立医療大学, 付属病院, 准教授 (30433155)
• Co-Investigator(Kenkyū-buntansha): 野口 恵美子 筑波大学, 医学医療系, 教授 (40344882) ; 岩崎 信明 茨城県立医療大学, 保健医療学部, 教授 (70251006)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: 熱性けいれん / 遺伝子 / エクソーム解析

Outline of Final Research Achievements

To identify febrile seizure susceptible genes, we performed whole exome sequencing of seven FS patients who belong to a large Japanese family with FS (KI#1). We extensively searched for candidate variants located in the FEB4 region, but no strong candidates were detected using our filtering method. We identified a heterozygous variant (c.3335A＞G; p.Ser1112Asn) in the sodium voltage-gated channel alpha subunit 9 gene (SCN9A) located on chromosome 2. Genotyping of this variant was performed for 270 subjects from Japanese families with FS. p.Ser1112Asn was not detected in any of the subjects analyzed except for the members from KI#1. Mutations in SCN9A have been reported to be associated with several disorders including FS and generalized epilepsy with febrile seizures plus. The functional effect of the variant remains to be elucidated. Experiments using model organisms may be required to examine the functional effect of the variant.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

熱性けいれんは良性の疾患と考えられているが、その一部はのちにてんかんを発症したり重積発作をひきおこすことがある。そのため、熱性けいれんの疾患感受性遺伝子を同定して病態を解明することが、てんかんなどのより重篤な疾患の病態解明につながる可能性が期待される。今回同定されたチャンネル遺伝子のバリアントは1家系のみにしか同定されていないが、同遺伝子の別のバリアントが他の日本人熱性けいれん家系の疾患発症にかかわっている可能性もあるため、今後さらに解析が必要と考えられた。