title: Evidence for a fourth locus for autosomal dominant nocturnal frontal lobe epilepsy.
abstract: Mutations responsible for autosomal dominant nocturnal frontal lobe epilepsy have been identified in two members of the neuronal nicotinic acetylcholine receptor gene family: CHRNA4(ENFL1 locus) and CHRNB2 (ENFL3 locus) coding for alpha4 and beta2 subunit, respectively. However, mutations in these genes account for only a minority (less than 10%) of cases. For a third ADNFLE locus (ENFL2) on chromosome 15q24 the gene was not identified. The involvement of the three loci in the pathogenesis of ADNFLE was investigated in 12 unrelated Italian families, selected on the basis of anamnestic and video-polysomnographic data. Compliant family members were typed for polymorphic markers spanning the analyzed chromosome regions. Linkage analyses excluded association of all chromosome regions with ADNFLE in 72% of cases. In two, four and one families it was impossible to ascertain or exclude association with ENFL1, ENFL2, or ENFL3, respectively, however, no mutations have been detected in the nicotinic receptor genes located in these regions. These data strongly suggest that ENFL1, ENFL2 and ENFL3 are minor loci for the disease and point to the existence of at least a fourth locus for ADNFLE.
authors.affiliation: Department of Biology and Genetics for Medical Sciences, University of Milan, Via Viotti 3/5, 20133 Milan, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Combi
authors.forename: Leda
authors.initials: L
authors.lastname: Dalprà
authors.forename: Massimo
authors.initials: M
authors.lastname: Malcovati
authors.forename: Alessandro
authors.initials: A
authors.lastname: Oldani
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Tenchini
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferini-Strambi
mesh_terms: D017034:Epilepsy, Frontal Lobe / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D040641:Quantitative Trait Loci / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics; D020919:Sleep Disorders, Intrinsic / Q000235:genetics*
chemical_list: D011978:Receptors, Nicotinic