Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 899-904 |
| Number of pages | 6 |
| Journal | Annals of Neurology |
| Volume | 58 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Dec 2005 |
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ASJC Scopus subject areas
- Neuroscience(all)
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Frontal lobe epilepsy and mutations of the corticotropin-releasing hormone gene. / Combi, Romina; Dalprà, Leda; Ferini-Strambi, Luigi; Tenchini, Maria L.
In: Annals of Neurology, Vol. 58, No. 6, 12.2005, p. 899-904.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Frontal lobe epilepsy and mutations of the corticotropin-releasing hormone gene
AU - Combi, Romina
AU - Dalprà, Leda
AU - Ferini-Strambi, Luigi
AU - Tenchini, Maria L.
PY - 2005/12
Y1 - 2005/12
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=28544440084&partnerID=8YFLogxK
U2 - 10.1002/ana.20660
DO - 10.1002/ana.20660
M3 - Article
C2 - 16222669
AN - SCOPUS:28544440084
VL - 58
SP - 899
EP - 904
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 6
ER -