Case Report: A 3' Splice Site Variation in Exon 3 Associated with Idiopathic Generalized Epilepsy in a Child

Overview

Journal Front Genet

Date 2025 Feb 3

PMID 39897619

Authors

Dandan Shi

Nannan Li

Caifang Fan

Qiang Luo

Affiliations

Soon will be listed here.

Abstract

The () gene plays a crucial role in neurodevelopment and is strongly associated with bipolar disorder, cognitive function, and Alzheimer's disease. Recently, has also emerged as a novel potential gene involved in generalized epilepsy and absence seizures. However, due to the complexity of gene function, reports on pathogenic variations of genes are still lacking. In this study, we present a case of a 5-year-old epilepsy patient. Through trio whole-exome sequencing, a heterozygous variant was identified at the splice site of 3' end of exon 3 in the gene (chr9:77249546, NM_006914.3: c.94-1G>A). This c.94-1G>A variant disrupts normal mRNA splicing, leading to the premature termination of the RORB protein. According to ACMG guidelines, this variant is classified as "likely pathogenic". Additionally, we provide a comprehensive summary of previously reported pathogenic or likely pathogenic variants in , contributing to the growing body of evidence linking this gene to epilepsy. Our findings offer valuable insights into the role of in epilepsy pathogenesis, and the splice site variant identified in this study further expands the mutational spectrum of the gene.

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