Autosomal Dominant Nocturnal Frontal Lobe Epilepsy in a Spanish Family With a Ser252Phe Mutation in the CHRNA4 Gene

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Abstract
Background A large family with autosomal dominant nocturnal frontal lobe epilepsy from the south of Spain was studied. The clinical appearance of the disease in this family, which included 28 members, of whom 11 were affected and 2 were obligate carriers, was identical to that previously described in an Australian family and a Norwegian family, in which mutations in exon 5 of theCHRNA4gene were found. Methods Following DNA extraction, the family was genotyped with 4 fluorescent markers flanking the locus to theCHRNA4gene on chromosome 20q13.3, and lod score computations were performed. The exon 5 of theCHRNA4gene was amplified between nucleotides 535 and 825 and polymerase chain reaction products were purified and sequenced directly. Results The same missense mutation as that found in the Australian family, C→T, which causes the replacement of a serine with phenylalanine in amino acid 252 in exon 5, was detected. This mutation segregated with the disorder in all 11 affected members, in the 2 obligate carriers, and in 1 asymptomatic sibling, and was not found in 1 spouse and 1 daughter. Neither of the 2 polymorphisms associated with this mutation in the Australian family were found, excluding a common ancestral haplotype for the 2 families. Conclusions These data confirm the clinical homogeneity in the phenotypic expression of autosomal dominant nocturnal frontal lobe epilepsy caused by mutation in theCHRNA4gene, and the pathogenic role of the Ser252Phe mutation in this disorder.