title: Functional characterization of a CRH missense mutation identified in an ADNFLE family.
abstract: 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.
authors.affiliation: Department of Surgery and Interdisciplinary Medicine, University of Milano-Bicocca, Monza, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Sansoni
authors.forename: Matilde
authors.initials: M
authors.lastname: Forcella
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mozzi
authors.forename: Paola
authors.initials: P
authors.lastname: Fusi
authors.forename: Roberto
authors.initials: R
authors.lastname: Ambrosini
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferini-Strambi
authors.forename: Romina
authors.initials: R
authors.lastname: Combi
mesh_terms: D000704:Analysis of Variance; D001483:Base Sequence; D015153:Blotting, Western; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D017034:Epilepsy, Frontal Lobe / Q000188:drug therapy / Q000235:genetics*; D005799:Genes, Dominant / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007558:Italy; D000077287:Levetiracetam; D008279:Magnetic Resonance Imaging; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010889:Piracetam / Q000031:analogs & derivatives / Q000627:therapeutic use; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D017931:DNA Primers; D000077287:Levetiracetam; D003346:Corticotropin-Releasing Hormone; D010889:Piracetam