Exome sequencing identified a novel missense mutation c.464G>A (p.G155D) in Ca-binding protein 4 () in a Chinese pedigree with autosomal dominant nocturnal frontal lobe epilepsy.

The aim of this study was to identify disease-causing gene mutations in a Chinese family affected with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), a 4-generation pedigree of 27 members in the Southern Chinese Han population, including 11 individuals diagnosed with ADNFLE. DNA samples were collected from 15 family members, chinese han people, including seven affected and eight unaffected individuals. None of these patients had night blindness or visual disorders. Four affected individuals were screened for mutations using whole-exome sequencing, and 13 potentially interesting mutations shared by all the four affected individuals were validated using the Sanger sequencing method. Only one novel missense mutation c.464G>A (p.G155D) in the gene, encoding the neuronal Ca-binding protein 4 (CaBP4), was present in all seven affected individuals in this family as revealed by PCR with blood DNA samples using primers. The mutation was also found in one young unaffected family member, but was absent from 300 unrelated control subjects. The p.G155D mutation, located near the Ca binding motif EF-hand 1 and the L-type Ca channel (Cav1.4) binding motif within the N-terminal lobe of CaBP4, is predicted to affect protein function according to the bioinformatics tools PolyPhen-2 and SIFT. These findings suggest that mutations in the gene may be linked to ADNFLE.