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.

Sansoni, V., Forcella, M., Mozzi, A., Fusi, P., Ambrosini, R., Ferini Strambi, L., et al. (2013). Functional Characterization of a CRH Missense Mutation Identified in an ADNFLE Family. PLOS ONE, 8(4), e61306 [10.1371/journal.pone.0061306].

Functional Characterization of a CRH Missense Mutation Identified in an ADNFLE Family

SANSONI, VERONICA;FORCELLA, MATILDE EMMA;MOZZI, ALESSANDRA;FUSI, PAOLA ALESSANDRA;AMBROSINI, ROBERTO;COMBI, ROMINA
2013

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.
Articolo in rivista - Articolo scientifico
Scientifica
ADNFLE; CRH; mutation; Epilepsy; gene
English
Sansoni, V., Forcella, M., Mozzi, A., Fusi, P., Ambrosini, R., Ferini Strambi, L., et al. (2013). Functional Characterization of a CRH Missense Mutation Identified in an ADNFLE Family. PLOS ONE, 8(4), e61306 [10.1371/journal.pone.0061306].
Sansoni, V; Forcella, M; Mozzi, A; Fusi, P; Ambrosini, R; Ferini Strambi, L; Combi, R
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/43426
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