Yan Hong-Jun, Wang Peng-Yu, Liu Wen-Hui, Gu Yu-Jie, Pan Jia-Cheng, Li Hua, Luo Sheng
Epilepsy Center, Guangdong Sanjiu Brain Hospital, Guangzhou, Guangdong, China.
Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
Hum Mutat. 2025 Feb 12;2025:9951922. doi: 10.1155/humu/9951922. eCollection 2025.
Genetic factors are estimated to contribute to 80% of people with epilepsy. However, only four genes were reported to be associated with temporal lobe epilepsy (TLE). This study is aimed at investigating the association between and TLE. Trio-based exome sequencing was performed in a patient, and a de novo variant was identified. The patient presented with TLE featuring by age of onset in juvenile, seizure-free status in adulthood, complications of memory decline and irritability, epileptic discharges in the bilateral temporal lobes, and bilateral hippocampal sclerosis. The pathogenicity of the identified variant was supposed by multiple pieces of evidence, including the missense tolerance ratio of 0%, high conservation of the affected residue, predicted to be "damaging" or "conserved" by 17 in silico tools, and classification of likely pathogenic variant by the American College of Medical Genetics and Genomics (ACMG) guidelines. Protein modeling indicated the alteration of protein structure and stability caused by the identified variant. The spatiotemporal expression of is consistent with the phenotypic features of this patient. This study suggested that is a novel candidate causative gene of TLE. The correlation between phenotypes and spatial-temporal expression provides a novel perspective for further exploration of the pathogenesis and prognosis of the disease.
据估计，80%的癫痫患者受遗传因素影响。然而，仅有四个基因被报道与颞叶癫痫（TLE）相关。本研究旨在探究[基因名称]与TLE之间的关联。对一名患者进行了基于三联体的外显子组测序，并鉴定出一个新生的[基因名称]变异。该患者表现为青少年起病的TLE，成年期无癫痫发作，伴有记忆衰退和易怒等并发症，双侧颞叶有癫痫放电，以及双侧海马硬化。通过多项证据推测所鉴定的[基因名称]变异具有致病性，包括错义耐受率为0%、受影响残基的高度保守性、17种计算机模拟工具预测为“有害”或“保守”，以及根据美国医学遗传学与基因组学学会（ACMG）指南分类为可能的致病变异。蛋白质建模表明所鉴定的变异导致了蛋白质结构和稳定性的改变。[基因名称]的时空表达与该患者的表型特征一致。本研究提示[基因名称]是TLE的一个新的候选致病基因。表型与时空表达之间的相关性为进一步探索该疾病的发病机制和预后提供了新的视角。
