てんかんの遺伝的背景・原因遺伝子・遺伝子治療

Epilepsy: Genetic Insights and Advances in Gene Therapies

てんかんの発症には遺伝的背景が大きく寄与することは一卵性双生児研究などからも明らかであり，これを含め，遺伝子診断・治療が急速に普及する近年，臨床医と患者家族，社会での正しい遺伝学的知識の共有が強く望まれる。本論ではてんかんの大規模全ゲノム解析や原因遺伝子EFHC1，SCN1A，SCN2Aなどの動物モデル解析や遺伝子治療法開発の試みなどについても紹介する。

Abstract

Studies on monozygotic twins, increased risk in children of affected parents, and the identification of numerous genes responsible for epilepsy and neurodevelopmental disorders, such as autism, intellectual disability, and schizophrenia, indicate that genetics play a major role in these diseases. Recent advancements in genetic testing and gene therapies have underscored the need for clinicians, patients, and family members to share accurate knowledge about the genetics of these conditions. In this review, I further discuss the results of studies on patients, mouse models of epilepsy, and neurodevelopmental disorder-related SCN1A, SCN2A, and STXBP1 genes, which encode voltage-gated sodium channel alpha subunits Nav1.1 and Nav1.2, as well as the synaptic protein Munc18-1. These studies suggest pathological mechanisms, including a novel cortico-striatal circuit, and trials aimed at developing gene therapies.