目的 探究1个癫痫伴发育迟缓及脑发育畸形家系的临床表现及致病基因变异情况。 方法 选取2022年7月2日于临沂市人民医院儿内科就诊的1个癫痫伴发育迟缓及脑发育异常家系为研究对象。收集患儿及其家系成员的临床资料，应用高通量测序技术对患儿及其姐姐与父母进行基因检测，采用Sanger测序法进行验证。 结果 患儿为6岁男性，自幼全面生长发育迟缓，间断抽搐4年余，癫痫发作存在热敏感特点，头颅影像学提示脑发育畸形，视频脑电图提示异常放电。高通量测序结果显示患儿及其姐姐均携带TUBB2A基因c.5G>T(p.Arg2Leu)杂合变异，其父母为野生型。根据美国医学遗传学与基因组学学会(ACMG)相关标准及指南，该变异评定为致病性变异(PS2＋PM2_Supporting＋PM5＋PP1＋PP2＋PP3)。 结论 TUBB2A基因c.5G>T(p.Arg2Leu)杂合变异考虑是该家系的遗传学病因，可能存在生殖腺细胞嵌合的情况。 Objective To explore the clinical manifestations and pathogenic variant in a family with epilepsy, developmental delay and brain deformity. Methods Clinical data of the child and his family members who had visited the Department of Pediatrics, Linyi People's Hospital on July 2, 2022 were collected. The child, his sister and parents were subjected to high-throughput sequencing, and the result was verified by Sanger sequencing. Results The child was a 6-year-old boy with developmentally delay and had epileptic seizures with fever sensitivity for four years. Cranial imaging showed brain dysplasia, while the video electroencephalogram showed abnormal discharge. High-throughput sequencing showed the child has harbored a heterozygous c. 5G>T (p.Arg2Leu) variant ofTUBB2A gene, which was unreported previously. His sister also carried the variant and had similar clinical manifestations, whilst his parents were of the wild-type and had normal clinical phenotypes. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS2+ PM2_Supporting+ PM5+ PP1+ PP2+ PP3). Conclusion The heterozygous c. 5G>T (p.Arg2Leu) variant of theTUBB2A gene, in the form of gonadal mosaicism, probably underlay the disorders in this family.
Genetic analysis of a family with epilepsy accompanied by developmental delay and brain deformity due to ade novo variant ofTUBB2A gene
Objective To explore the clinical manifestations and pathogenic variant in a family with epilepsy, developmental delay and brain deformity. Methods Clinical data of the child and his family members who had visited the Department of Pediatrics, Linyi People's Hospital on July 2, 2022 were collected. The child, his sister and parents were subjected to high-throughput sequencing, and the result was verified by Sanger sequencing. Results The child was a 6-year-old boy with developmentally delay and had epileptic seizures with fever sensitivity for four years. Cranial imaging showed brain dysplasia, while the video electroencephalogram showed abnormal discharge. High-throughput sequencing showed the child has harbored a heterozygous c. 5G>T (p.Arg2Leu) variant ofTUBB2A gene, which was unreported previously. His sister also carried the variant and had similar clinical manifestations, whilst his parents were of the wild-type and had normal clinical phenotypes. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS2+ PM2_Supporting+ PM5+ PP1+ PP2+ PP3). Conclusion The heterozygous c. 5G>T (p.Arg2Leu) variant of theTUBB2A gene, in the form of gonadal mosaicism, probably underlay the disorders in this family.
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