A new locus for autosomal dominant nocturnal frontal lobe epilepsy maps tochromosome 1

Background: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is caused by mutations in the alpha4 subunit of the neuronal nicotinic acetylc holine receptor (CHRNA4) gene, mapping on chromosome 20q13.2. A second ADNF LE locus was mapped on chromosome 15q24. Objective: To report a new third A DNFLE locus on chromosome 1 in a large Italian family. Methods: The authors performed a clinical and genetic study in a large, three-generation ADNFLE family from southern Italy, including eight affected individuals and three obligate carriers. Results: The age at onset of seizures was around 9 year s of age and all affected individuals manifested nocturnal partial seizures of frontal lobe origin. Interictal awake and sleep EEG recordings showed n o definite epileptiform abnormalities in most patients. Ictal video-EEG sho wed that the attacks were partial seizures with a frontal lobe semiology. I ntellectual and neurologic examinations, and brain CT or MRI results were a lways normal. Carbamazepine was effective in all treated patients. Exclusio n mapping of the known loci linked to ADNFLE-ENFL1, and ENFL2, on chromosom es 20q13.2 and 15q24-was performed on the pedigree before starting the geno me-wide linkage analysis. The whole genome scan mapping allowed the identif ication of a new ADNFLE locus spanning the pericentromeric region of chromo some I. Conclusions: The authors provided evidence for a third locus associ ated to autosomal dominant nocturnal frontal lobe epilepsy on chromosome 1. Among the known genes mapping within this critical region, the beta2 subun it of the nicotinic receptor (CHRNB2) represents the most obvious candidate .