遗传性全面性癫痫的分子遗传学研究进展

Advance in molecular genetic research on generalized epilepsies

遗传性全面性癫痫(genetic generalized epilepsies,GGEs)是一类主要由遗传因素决定的癫痫综合征,少数遵循孟德尔遗传规律,大部分则表现为多基因遗传。研究者最初发现与GGEs相关的基因大多涉及离子通道,包括电压门控的钠离子、钾离子、钙离子、氯离子通道以及配体门控的γ-氨基丁酸受体通道,进一步研究发现一些非离子通道基因也与GGEs有关,并且新生突变和拷贝数变异也在GGEs发病中具有重要的作用。近年来,二代测序和三代测序的运用推动了GGEs分子遗传学的探索进程,但也带来了更多的挑战。这些遗传学上的发现对阐明GGEs发病机制、临床诊断以及探索精准治疗提供了重要基础。本文就GGEs的分子遗传学研究进展进行综述。

Genetic generalized epilepsies (GGEs)are a group of epilepsy syndromes caused by genetic factors.A few of GGEs conform to the Mendelian patterns,while most of them show polygene inheritance. Researchers initially found that most of the genes associated with GGEs are related to ion channels including voltage-gated sodium channels,potassium channels,calcium channels and chloride channels,and ligand-gated γ-aminobutyric acid receptor channels.Further researches have shown that certain non-ion channel genes are also related to GGEs,and that de novo mutations and copy number variants also play an important role in the pathogenesis of GGEs.Application of next-and third-generation sequencing promoted delineation of the molecular genetics of the GGEs,but also brought more challenges.Genetic findings have provided an important basis for the elucidation of the pathogenesis,clinical diagnosis and precise treatment of GGEs. This paper provided a review for recent progress made in molecular genetics of GGEs.