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

Abstract

These data confirm the clinical homogeneity in the phenotypic expression of autosomal dominant nocturnal frontal lobe epilepsy caused by mutation in the CHRNA4 gene, and the pathogenic role of the Ser252Phe mutation in this disorder.

The Juvenile Myoclonic Epilepsy GABAAReceptor α1 Subunit Mutation A322D Produces Asymmetrical, Subunit Position-Dependent Reduction of Heterozygous Receptor Currents and α1 Subunit Protein Expression

“…The epilepsy syndromes, benign familial neonatal seizures, and autosomal dominant nocturnal frontal lobe epilepsy are associated with mutations of voltage-gated potassium channels (Biervert et al, 1998;Singh et al, 1998;Dedek et al, 2001) and AChR channels (Steinlein et al, 1995(Steinlein et al, , 1997Hirose et al, 1999;Saenz et al, 1999;De Fusco et al, 2000;Phillips et al, 2000Phillips et al, , 2001, respectively. Both of these ion channels are multimeric proteins, and in both cases, the mutated subunit is present in greater than one copy within the protein complex.…”

Nocturnal Frontal Lobe Epilepsy

“…Both mutations were shown to have major effects on receptor function in vitro [23][24][25][26]. With the identification of these mutations, subsequently confirmed in families of different origins [27][28][29], ADNFLE became the first epilepsy in which genetic bases were detected, apparently showing features of a monogenic disease. Three de novo or inherited CHRNA4 mutations, occasionally associated with mild-to-moderate mental retardation were later reported [15,[30][31][32][33][34][35][36][37].…”

Autosomal dominant nocturnal frontal lobe epilepsy: a genotypic comparative study of Japanese and Korean families carrying the CHRNA4 Ser284Leu mutation

“…10 Approximately 10-20% of patients have a positive family history and fewer than 5% a negative one. 11 Among the four mutations in CHRNA4 (Ser280Phe, Ser284Leu, Leu291dup and Thr293Ile), Ser280Phe and Ser284Leu have been identified in several unrelated families (mutation names may be different from those of previous papers; we use NP_000735.1): the Ser280Phe in an Australian, Spanish, Norwegian and Scottish families, [12][13][14][15] and the Ser284Leu in a Japanese, Korean, Polish and Lebanese families. [16][17][18][19] It has been assumed that founder effect is not relevant to ADNFLE, because most of the families studied come from different countries, 20 and a previous haplotype study of the Australian and Norwegian family 14 showed no genetic connection.…”