Analiza genetyczna zmian w genie u dzieci z epilepsją: związek między genotypem a objawami klinicznymi

BACKGROUND: Variants in are associated with a rare autosomal dominant neurodevelopmental disorder that includes developmental delay and epilepsy. However, the phenotypic spectrum resulting from variants is broad, and the genotype-phenotype correlation for -related diseases remains elusive. Our objective was to investigate variants in an epilepsy cohort and explore the genotype-phenotype correlation of through a literature review. METHODS: A total of 571 eligible children with epilepsy were enrolled in the study. Whole exome sequencing (WES) was conducted to analyze variations in the gene, and computational predictions and pathogenicity analyses were performed on the identified potential pathogenic variants. Additionally, a literature review and phenotypic similarity analysis were conducted to investigate the genotype-phenotype correlation of the gene. RESULT: We identified two patients with heterozygous pathogenic variants (Proband 1: c.1396C > G, p.His466Asp; Proband 2: c.1463_1467dup, p.Pro490AlafsTer25). Proband 1 was suspected of having underlying developmental delay. Literature review showed that variants are associated with a wide range of phenotypes. Patients with nonsense variants exhibited highly similar phenotypes. Missense variants tended to present with epilepsy as the initial symptom, whereas nonsense variants often began with different forms of developmental delay or regression. CONCLUSIONS: We identified two variants in the pediatric epilepsy cohort, contributing to the expansion of its variant and phenotypic spectrum. Furthermore, we found that patient phenotypes associated with variants are linked to specific types of variants in the gene.