DOI: 10.1177/19450265261503187 ISSN: 1945-0265
Genetic Analysis of
IRF2BPL
in Children with Epilepsy: Genotypic and Phenotypic Correlation
Shuyue Zhang, Shaopei Chen, Chunyu Gu, Xiayue Zhang, Dong Li, Chunquan Cai, Bo wu, Jianbo Shu
Background:
Variants in
IRF2BPL
are associated with a rare autosomal dominant neurodevelopmental disorder that includes developmental delay and epilepsy. However, the phenotypic spectrum resulting from
IRF2BPL
variants is broad, and the genotype-phenotype correlation for
IRF2BPL
-related diseases remains elusive. Our objective was to investigate
IRF2BPL
variants in an epilepsy cohort and explore the genotype-phenotype correlation of
IRF2BPL
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
IRF2BPL
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
IRF2BPL
gene.
Result:
We identified two patients with
de novo
heterozygous pathogenic
IRF2BPL
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
IRF2BPL
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
de novo IRF2BPL
variants in the pediatric epilepsy cohort, contributing to the expansion of its variant and phenotypic spectrum. Furthermore, we found that patient phenotypes associated with
IRF2BPL
variants are linked to specific types of variants in the
IRF2BPL
gene.