title: Frontal lobe epilepsy and mutations of the corticotropin-releasing hormone gene.
abstract: Nocturnal frontal lobe epilepsy up to now has been considered a channelopathy caused by mutations in the alpha(4) and beta(2) subunits of the neuronal nicotinic acetylcholine receptor. However, these mutations account for only a minority of patients, and the existence of at least a new locus for the disease has been demonstrated. In one Italian nocturnal frontal lobe epilepsy family, we identified two new putative loci on chromosomes 3 and 8, where several candidate genes are mapped. In particular, on chromosome 8, corticotropin-releasing hormone gene (CRH) appears to be a good candidate. We therefore searched for CRH mutations in the proband. The study allowed the identification of a nucleotide variation in the promoter that was subsequently detected in all affected and obligate carrier members of the same family, in two sporadic cases, in all affected members of an additional compliant family, and in the proband of a noncompliant family. Moreover, a different mutation in the promoter was detected in a familial case. In vitro experiments showed altered levels of gene expression. CRH alterations could explain several autosomal dominant nocturnal frontal lobe epilepsy clinical features.
authors.affiliation: Department of Biology and Genetics for Medical Sciences, University of Milan, Milan, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Combi
authors.forename: Leda
authors.initials: L
authors.lastname: Dalprà
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferini-Strambi
authors.forename: Maria L
authors.initials: ML
authors.lastname: Tenchini
mesh_terms: D000818:Animals; D002898:Chromosomes, Human, Pair 8; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D004569:Electroencephalography; D017034:Epilepsy, Frontal Lobe / Q000175:diagnosis / Q000235:genetics*; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D006801:Humans; D006822:Hybrid Cells; D007558:Italy; D008297:Male; D051379:Mice; D009447:Neuroblastoma; D010375:Pedigree; D017354:Point Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D014162:Transfection
chemical_list: D003346:Corticotropin-Releasing Hormone