EXON-INTRON STRUCTURE OF THE HUMAN NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTOR ALPHA-4 SUBUNIT (CHRNA4)

The human neuronal nicotinic acetylcholine receptor alpha 4 subunit ge ne (CHRNA4) is located in the candidate region for three different phe notype: benign familial neonatal convulsions, autosomal dominant noctu rnal frontal lobe epilepsy, and low-voltage EEG. Recently, a missense mutation in transmembrane domain 2 of CHRNA4 was found to be associate d with autosomal dominant nocturnal frontal lobe epilepsy in one exten ded pedigree. We have determined the genomic organization of CHRNA4, w hich consists of six exons distributed over approximately 17 kb of gen omic DNA. The nucleotide sequence obtained from the genomic regions ad jacent to the exon boundaries enabled us to develop a set of primer pa irs for PCR amplification of the complete coding region. The sequence analysis provides the basis for a comprehensive mutation screening of CHRNA4 in the above-mentioned phenotypes and possibly in other types o f idiopathic epilepsies. (C) 1996 Academic Press, Inc.