Frontal lobe epilepsy and mutations of the corticotropin-releasing hormone gene

Nocturnal frontal lobe epilepsy up to now has been considered a channelopathy caused by mutations in the α4 and β2 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 ha...

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Bibliographic Details
Published in:Annals of neurology 2005-12, Vol.58 (6), p.899-904
Main Authors: Combi, Romina, Dalprà, Leda, Ferini-Strambi, Luigi, Tenchini, Maria L.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Chromosomes, Human, Pair 8
Corticotropin-Releasing Hormone - genetics
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Electroencephalography
Epilepsy, Frontal Lobe - diagnosis
Epilepsy, Frontal Lobe - genetics
Family Health
Female
Gene Frequency
Genetic Testing
Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy
Humans
Hybrid Cells
Italy
Male
Medical sciences
Mice
Nervous system (semeiology, syndromes)
Neuroblastoma
Neurology
Pedigree
Point Mutation
Promoter Regions, Genetic - genetics
Rats
Transfection
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Summary:Nocturnal frontal lobe epilepsy up to now has been considered a channelopathy caused by mutations in the α4 and β2 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. Ann Neurol 2006
ISSN:0364-5134
1531-8249
DOI:10.1002/ana.20660