Variants of TSC1 are associated with developmental and epileptic encephalopathy and focal epilepsy without tuberous sclerosis  

作　　者：Nanxiang Shen Zhihong Zhuo Xiangyun Luo Bingmei Li Xuqing Lin Sheng Luo Zilong Ye Pengyu Wang Na He Yiwu Shi Weiping Liao 

机构地区：[1]Department of Neurology,Institute of Neuroscience,Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China,The Second Afliated Hospital,Guangzhou Medical University,Guangzhou 510260,China [2]Department of Pediatrics,The First Afliated Hospital of Zhengzhou University,Zhengzhou 450003,China [3]Guangzhou Medical University,Guangzhou 511436,China.

出　　处：《Acta Epileptologica》2024年第4期336-342,共7页癫痫学报(英文)

基　　金：supported by the National Natural Science Foundation of China(82271505);Guangzhou Medical University Student Innovation Ability Promoting Program(2022A045).

摘　　要：Background The TSC1 gene encodes a growth inhibitory protein hamartin,which plays a crucial role in negative regulation of the activity of mTORC1(mechanistic target of rapamycin complex 1).TSC1 has been associated with tuberous sclerosis complex(TSC).This study aims to investigate the association between TSC1 variants and common epilepsy.Methods Trio-based whole-exome sequencing was performed in epilepsy patients without acquired etiologies from the China Epilepsy Gene 1.0 Project platform.The pathogenicity of the variants was evaluated according to the American College of Medical Genetics and Genomic(ACMG)guidelines.Results Two TSC1 de novo variants,including c.1498 C>T/p.Arg500*and c.2356 C>T/p.Arg786*,were identifed in two patients with developmental and epileptic encephalopathy(DEE).The patients exhibited frequent seizures and neurodevelopmental delay.Additionally,we identifed two heterozygous TSC1 variants that afected four individuals with focal epilepsy from two unrelated families.The four probands did not present any typical symptom of TSC and had normal brain MRI fndings.The four variants were absent in the Genome Aggregation Database(gnomAD)and were predicted to be damaging with a in silico prediction tool.Based on the ACMG guidelines,the four variants were evaluated to be“pathogenic”or“likely pathogenic”.Of the patients in the China Epilepsy Gene 1.0 Project,22 patients carried TSC1 variants and were diagnosed with TSC.The ratio of patients carrying TSC1 variants with or without TSC is about 5:1.Conclusions TSC1 is potentially associated with common epilepsy without tuberous sclerosis.

关 键 词：TSC1 gene De novo variant Focal epilepsy Developmental and epileptic encephalopathy 

分 类 号：R74[医药卫生—神经病学与精神病学]