A novel CACNA1E mutation (c.1256G > A) was identified in a Chinese patient with epilepsy and congenital heart disease
Background CACNA1E mutations cause developmental and epileptic encephalopathy. We report a Chinese pediatric patient with epilepsy and congenital heart disease who carries a novel CACNA1E variant. Methods Whole-exome sequencing (WES) was performed on the proband and his unaffected parents. The variant was validated by Sanger sequencing and screened in 200 healthy controls. Bioinformatic tools and ACMG criteria were used for pathogenicity assessment. Results A de novo heterozygous missense variant, NM_000721.4: c.1256G > A (p.R419Q), was identified. It was absent in both parents and in 200 controls. The variant lies in a highly conserved and intolerant region. ACMG classification: likely pathogenic (PS2 + PM2 + PP3). The patient showed marked short-term response to adrenocorticotropic hormone (ACTH). Conclusion This novel variant expands the mutational spectrum of CACNA1E and provides a potential treatment clue for ACTH responsiveness in CACNA1E-related spasms.