A Spanish Family with Autosomal Dominant Nocturnal Frontal Lobe Epilepsy and a Mutation in the CHRNB2 Gene.
Abstract number :
1.056
Submission category :
Year :
2001
Submission ID :
412
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
F. Diaz-Otero, MD, Neurology, Fundacion Jimenez Diaz, Madrid, Spain; J. Morales, BSc, Neurology, Fundacion Jimenez Diaz, Madrid, Spain; M. Quesada, MD, Neurophysiology, Hospital Virgen de la Macarena, Sevilla, Spain; C. Martinez-Parra, MD, Neurology, Hosp
RATIONALE: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an idiopathic partial epilepsy characterized by clustered attacks of frontal lobe seizures during sleep. ADNFLE has been associated with mutations in the gene coding for the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4). Recently, two mutations in the gene coding for the beta2 subunit (CHRNB2) have been reported in two ADNFLE families (De Fusco et al, 2000 and Phillips et al, 2001). Here we describe a family from southern Spain including six affected individuals and three obligate carriers in which we detected one of the two described mutations (G748A) in the CHRNB2 gene. At the time of this writing, this family represents the third ADNFLE family with mutations in the CHRNB2 gene and the second with the G748A mutation.
METHODS: A three generation ADNFLE Spanish family was identified through a 15 year old proband with a history of nocturnal frontal lobe seizures since the age of 3 years. In addition to the proband, five other affected members belonging to three generations were identified. Personal interviews and genetic analysis were carried out in 16 individuals. Electroencephalographic (EEG) or Video-EEG recordings and MRI studies were performed in all affected individuals. Parts of the coding region of the CHRNB2 gene were sequenced in all 16 individuals.
RESULTS: All affected members presented the clinical characteristics of ADNFLE. The mean age at onset of seizures was 8.4 years of age and all affected individuals manifested nocturnal partial seizures of frontal lobe origin. Interictal awake and sleep EEG recordings showed no definite epileptiform abnormalities in most patients. Ictal video-EEG recordings showed that the attacks were partial seizures with a frontal lobe semiology. Mutation analysis of the CHRNB2 gene revealed the presence of a G-to-A transition (G748A), affecting a V287M substitution within the M2 domain, on one allele of all affected individuals. Three obligate carriers presented the mutation and had no symptoms of the disease. Careful analysis of the clinical phenotype did not reveal specific characteristics inherent to mutations in the CHRNB2 gene.
CONCLUSIONS: An additional ADNFLE family with the G748A mutation in the CHRNB2 gene is presented. The clinical phenotype appears to be similar to that described for ADNFLE associated with mutations in the CHRNA4 gene, suggesting that mutations in the genes coding for the alpha4 and beta2 subunits of the neuronal nicotinic acetylcholine receptor lead to similar functional alterations.
Support: Spanish Ministry of Science and Technology SAF2000-0012.