Epilepsy Research (2007) 74, 70—73 journal homepage: www.elsevier.com/locate/epilepsyres SHORT COMMUNICATION Further evidence of genetic heterogeneity in families with autosomal dominant nocturnal frontal lobe epilepsy Elvira V. De Marco a , Antonio Gambardella a,b,* , Ferdinanda Annesi a , Angelo Labate a,b , Sara Carrideo a , Paola Forabosco c , Donatella Civitelli a , Innocenza C. Cir` o Candiano a , Patrizia Tarantino a , Grazia Annesi a , Aldo Quattrone a,b a Institute of Neurological Sciences, National Research Council, Mangone (CS), Italy b Institute of Neurology, University Magna Graecia Catanzaro, Italy c Institute of Population Genetics, National Research Council, Alghero (SS), Italy Received 19 July 2006; received in revised form 5 December 2006; accepted 23 December 2006 Available online 26 February 2007 KEYWORDS Nocturnal frontal lobe epilepsy; Genetics; Nicotinic receptors Abstract Purpose: Mutations in the genes encoding the alfa 2 , alfa 4 and beta 2 subunits of the neuronal nicotinic acetylcholine receptor (nAChR) play a causative role in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Moreover, variations in the promoter of the corticotropic- releasing hormone gene (CRH) were also associated with ADNFLE. Here, we investigated whether nine brain-expressed genes (CHRNA2, CHRNA3, CHRNA4, CHRNA5, CHRNA6, CHRNA7, CHRNB2, CHRNB3, CHRNB4), encoding distinct nAChR subunits, and CRH are associated with the disease in three distinct ADNFLE families from Southern Italy. Methods: There were 14 living affected individuals (9 women), ranging in age from 14 to 57 years, pertaining to three unrelated families. Age at onset of seizures clustered around 9 years of age (range from 7 and 16 years, mean: 9.1 years ± 3.8). All affected individuals manifested nocturnal partial seizures of frontal lobe origin, which were well controlled by medications. Exon 5 of CHRNA4 and CHRNB2 genes, harboring all the known mutations, was sequenced in the probands. Then, we performed a linkage study on 13 affected and 26 non-affected individuals belonging to the three families with microsatellite markers and an intragenic polymorphisms encompassing the chromosome localization of the nAChR subunit genes and of the CRH gene. ∗ Corresponding author at: Cattedra ed U.O. di Neurologia, Facolt` a di Medicina e Chirurgia ‘‘Magna Graecia’’ Catanzaro, Policlinico Universitario Mater Domini, Viale Europa, Localit` a Germaneto, 88100 Catanzaro, Italy. Tel.: +39 0961 3647270; fax: +39 0961 3697177. E-mail address: a.gambardella@isn.cnr.it (A. Gambardella). 0920-1211/$ — see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.eplepsyres.2006.12.006