http://www.cnr.it/ontology/cnr/individuo/prodotto/ID50046
Further evidence of genetic heterogeneity in families with autosomal dominant nocturnal frontal lobe epilepsy. (Articolo in rivista)
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- Label
- Further evidence of genetic heterogeneity in families with autosomal dominant nocturnal frontal lobe epilepsy. (Articolo in rivista) (literal)
- Anno
- 2007-01-01T00:00:00+01:00 (literal)
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- De Marco EV; Gambardella A; Annesi F; Labate A; Carrideo S; Forabosco P; Civitelli D; Candiano IC; Tarantino P; Annesi G; Quattrone A (literal)
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- ISI Web of Science (WOS) (literal)
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- Institute of Neurological Sciences, National Research Council, Mangone (CS), Italy
Institute of Neurology, University Magna Graecia Catanzaro, Italy
Institute of Population Genetics, National Research Council, Alghero (SS), Italy (literal)
- Titolo
- Further evidence of genetic heterogeneity in families with autosomal dominant nocturnal frontal lobe epilepsy. (literal)
- Abstract
- PURPOSE: Mutations in the genes encoding the alfa(2), alfa(4) and beta(2) subunits of the neuronal nicotinic acetylcholine receptor (nAChR) play a causative role in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Moreover, variations in the promoter of the corticotropic-releasing hormone gene (CRH) were also associated with ADNFLE. Here, we investigated whether nine brain-expressed genes (CHRNA2, CHRNA3, CHRNA4, CHRNA5, CHRNA6, CHRNA7, CHRNB2, CHRNB3, CHRNB4), encoding distinct nAChR subunits, and CRH are associated with the disease in three distinct ADNFLE families from Southern Italy. METHODS: There were 14 living affected individuals (9 women), ranging in age from 14 to 57 years, pertaining to three unrelated families. Age at onset of seizures clustered around 9 years of age (range from 7 and 16 years, mean: 9.1 years+/-3.8). All affected individuals manifested nocturnal partial seizures of frontal lobe origin, which were well controlled by medications. Exon 5 of CHRNA4 and CHRNB2 genes, harboring all the known mutations, was sequenced in the probands. Then, we performed a linkage study on 13 affected and 26 non-affected individuals belonging to the three families with microsatellite markers and an intragenic polymorphisms encompassing the chromosome localization of the nAChR subunit genes and of the CRH gene. RESULTS: Mutational and linkage analyses allowed us to exclude the involvement of all known nAChR subunit genes and of the CRH gene in ADNFLE in our families. CONCLUSION: Our results further illustrate the considerable genetic heterogeneity for such a syndrome, despite the quite homogeneous clinical picture. It is therefore reasonable to hypothesize that at least another gene not belonging to the nAChR gene family, in addition to CRH, is involved in the pathogenesis of ADNFLE. (literal)
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