Nocturnal frontal lobe epilepsy has been historically considered a channelopathy caused by mutations in subunits of the neuronal nicotinic acetylcholine receptor or in a recently reported potassium channel. 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 2005, we detected two nucleotide variations in the promoter of the CRH gene coding for the corticotropin releasing hormone in 7 patients. These variations cosegregated with the disease and were demonstrated to alter the cellular levels of this hormone. Here, we report the identification in an Italian affected family of a novel missense mutation (hpreproCRH p.Pro30Arg) located in the region of the CRH coding for the protein pro-sequence. The mutation was detected in heterozygosity in the two affected individuals. In vitro assays demonstrated that this mutation results in reduced levels of protein secretion in the short time thus suggesting that mutated people could present an altered capability to respond immediately to stress agents.
Functional Characterization of a CRH Missense Mutation Identified in an ADNFLE Family / V. Sansoni, M. Forcella, A. Mozzi, P. Fusi, R. Ambrosini, L. Ferini-Strambi, R. Combi. - In: PLOS ONE. - ISSN 1932-6203. - 8:4(2013 Apr 11).
|Titolo:||Functional Characterization of a CRH Missense Mutation Identified in an ADNFLE Family|
|Parole Chiave:||Analysis of Variance; Base Sequence; Blotting, Western; Corticotropin-Releasing Hormone; DNA Primers; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Epilepsy, Frontal Lobe; Genes, Dominant; Genetic Vectors; Heterozygote; Humans; Italy; Magnetic Resonance Imaging; Microscopy, Fluorescence; Molecular Sequence Data; Mutation, Missense; Pedigree; Piracetam; Real-Time Polymerase Chain Reaction; Sequence Analysis, DNA; Medicine (all); Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all)|
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
|Data di pubblicazione:||11-apr-2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1371/journal.pone.0061306|
|Appare nelle tipologie:||01 - Articolo su periodico|
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