Two novel variants of the STXBP1 and CHRNB2 genes identified in a Chinese boy with refractory seizures and developmental delay.

Abstract

Autosomal dominant sleep-related hypermotor epilepsy is a rare disease caused by pathogenic variants of CHRNB2, CHRNA4, and CHRNA2 genes, with nocturnal frontal lobe epilepsy as the main symptoms. Syntaxin binding protein 1 (STXBP1) gene mutation can cause developmental and epileptic encephalopathy 4, mainly presenting as a developmental and epileptic encephalopathy. We performed the exome-targeted next-generation sequencing in our patient and identified two heterozygous variants: c.963 + 2T>C of STXBP1 and c.520_527delinsTGCTAC (p.R174Cfs*16) of CHRNB2. Molecular analysis was performed of the variant c.963 + 2T>C. Aberrantly spliced products were observed, proving the pathogenicity of this variant. Refractory seizures and developmental delay could be explained. Although the variant c.520_527delinsTGCTAC could cause the truncation of the proteins, it was ultimately determined to be nonpathogenic. The startle-like responses that occurred occasionally during the night were ultimately determined to be an uncommon phenotype caused by the STXBP1 variant.