Mutational analysis of CHRNB2, CHRNA2 and CHRNA4 genes in Chinese population with autosomal dominant nocturnal frontal lobe epilepsy

Objective: The present study aims to investigate the gene mutations of CHRNB2, CHRNA2 and CHRNA4 in Chinese population with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Methods: 257 ADNFLE patients (74 sporadic and 32 familial) were collected, including 42 pedigree patients and 215 sporadic cases. Exon mutational screening of CHRNB2, CHRNA2 and CHRNA4 was performed by direct PCR sequencing. Results: No published mutations of CHRNB2, CHRNA4 and CHRNA2 genes were detected in this study. Three kinds of c. SNP (c.66C> T, c.249C> T, c.375A> G) were detected on the 2nd and 5th exons of CHRNA2; six kinds of c. SNP (c.639T> C, c.678T> C, c.1209G> T, c.1227T> C, c.1659G> A, c.1629C> T) were detected on the 5th exon of CHRNA4. Three novel mutations were discovered, respectively locating on the exon 5 of CHRNA4 gene (c.570C> T), 5th and 6th exons of CHRNB2 gene (c.483C> T and c.1407C> G). The three mutations were absent in 200 healthy controls, indicating that the mutations were very rare. Conclusion: CHRNA4, CHRNB2 and CHRNA2 may be not the causative genes of Chinese ADNFLE population. Whether the three novel synonymous mutations were genetic factors of ADNFLE pathogenesis in Chinese Han population needs to be further studied.