2例RYR2基因突变致癫痫患儿的临床及基因型特征分析

Clinical and genotype features of 2 infants with epilepsy caused by RYR2 gene mutations

目的分析RYR2基因突变致婴儿癫痫的临床及基因型特征,探讨RYR2基因突变和癫痫的相关性。方法回顾性分析郑州大学第一附属医院儿科于2020年12月、2022年5月收治的2例癫痫伴RYR2基因突变婴儿的临床资料、基因检测结果,并进行文献复习。结果2例患儿的起病年龄均为婴儿期(出生后4个月、9个月),表现为反复抽搐,发作时无诱因,1例动态心电图检查异常但无恶性室性心律失常,1例发作间期脑电图示异常放电,应用左乙拉西坦口服液治疗后发作均得到有效控制。全外显子测序发现1例患儿RYR2基因c.14767A>G(p.Met4923Val)杂合错义变异,1例患儿RYR2基因c.14014A>G(p.Met4672Val)杂合错义变异,2例患儿均未发现其他已知癫痫致病基因突变。美国医学遗传学与基因组学会指南评价2个变异均为致病性突变(PS2+PM1+PM2+PP2+PP3)。结论RYR2基因可能是一种新的癫痫致病基因。

Objective To analyze the clinical and genotype features of infants with epilepsy caused by RYR2 gene mutations,and explore the correlation between RYR2 gene mutations and epilepsy.Methods The clinical characteristics and genetic test results of 2 infants with epilepsy caused by RYR2 gene mutations,admitted to Department of Pediatrics,First Affiliated Hospital of Zhengzhou University in December 2020 or May 2022,were retrospectively analyzed.The related literature was reviewed.Results These 2 infants had onset at the infancy(4 and 9 months after birth),characterized by repeated unprovoked seizures;1 patient had abnormal dynamic electrocardiogram results without malignant ventricular arrhythmia;1 patient showed abnormal discharge in interictal electroencephalogram,which was effectively controlled after treatment with levetiracetam oral solution.Whole exon sequencing revealed heterozygous missense mutation of the RYR2 gene c.14767A>G(p.Met4923Val)in 1 child,heterozygous missense mutation of the RYR2 gene c.14014A>G(p.Met4672Val)in 1 child,and no other known epilepsy pathogenic gene mutation was found in 2 children.American Society for Medical Genetics and Genomics guidelines evaluated 2 mutations as pathogenic mutations(PS2+PM1+PM2+PP2+PP3).Conclusion RYR2 gene is potentially a novel epilepsy gene.