[Genetic analysis of a family with epilepsy accompanied by developmental delay and brain deformity due to a de novo variant of TUBB2A 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 of TUBB2A 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 the TUBB2A gene, in the form of gonadal mosaicism, probably underlay the disorders in this family.