Abstract
Sleep has traditionally been recognized as a precipitating factor for some forms of epilepsy, although differential diagnosis between some seizure types and parasomnias may be difficult. Autosomal dominant frontal lobe epilepsy is characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements and has been associated with mutations of the α4 and β2 subunits of the neuronal nicotinic acetylcholine receptor. We performed a clinical and molecular genetic study of a large pedigree segregating sleep-related epilepsy in which seizures are associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking. We identified a new genetic locus for familial sleep-related focal epilepsy on chromosome 8p12.3-8q12.3. By sequencing the positional candidate neuronal cholinergic receptor α2 subunit gene (CHRNA2), we detected a heterozygous missense mutation, I279N, in the first transmembrane domain that is crucial for receptor function. Whole-cell recordings of transiently transfected HEK293 cells expressing either the mutant or the wild-type receptor showed that the new CHRNA2 mutation markedly increases the receptor sensitivity to acetylcholine, therefore indicating that the nicotinic α2 subunit alteration is the underlying cause. CHRNA2 is the third neuronal cholinergic receptor gene to be associated with familial sleep-related epilepsies. Compared with the CHRNA4 and CHRNB2 mutations reported elsewhere, CHRNA2 mutations cause a more complex and finalized ictal behavior.
| Original language | English |
|---|---|
| Pages (from-to) | 342-350 |
| Number of pages | 9 |
| Journal | American Journal of Human Genetics |
| Volume | 79 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Aug 2006 |
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ASJC Scopus subject areas
- Genetics
Cite this
Increased sensitivity of the neuronal nicotinic receptor α2 subunit causes familial epilepsy with nocturnal wandering and ictal fear. / Aridon, Paolo; Marini, Carla; Resta, Chiara Di; Brilli, Elisa; De Fusco, Maurizio; Politi, Fausta; Parrini, Elena; Manfredi, Irene; Pisano, Tiziana; Pruna, Dario; Curia, Giulia; Cianchetti, Carlo; Pasqualetti, Massimo; Becchetti, Andrea; Guerrini, Renzo; Casari, Giorgio.
In: American Journal of Human Genetics, Vol. 79, No. 2, 08.2006, p. 342-350.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Increased sensitivity of the neuronal nicotinic receptor α2 subunit causes familial epilepsy with nocturnal wandering and ictal fear
AU - Aridon, Paolo
AU - Marini, Carla
AU - Resta, Chiara Di
AU - Brilli, Elisa
AU - De Fusco, Maurizio
AU - Politi, Fausta
AU - Parrini, Elena
AU - Manfredi, Irene
AU - Pisano, Tiziana
AU - Pruna, Dario
AU - Curia, Giulia
AU - Cianchetti, Carlo
AU - Pasqualetti, Massimo
AU - Becchetti, Andrea
AU - Guerrini, Renzo
AU - Casari, Giorgio
PY - 2006/8
Y1 - 2006/8
N2 - Sleep has traditionally been recognized as a precipitating factor for some forms of epilepsy, although differential diagnosis between some seizure types and parasomnias may be difficult. Autosomal dominant frontal lobe epilepsy is characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements and has been associated with mutations of the α4 and β2 subunits of the neuronal nicotinic acetylcholine receptor. We performed a clinical and molecular genetic study of a large pedigree segregating sleep-related epilepsy in which seizures are associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking. We identified a new genetic locus for familial sleep-related focal epilepsy on chromosome 8p12.3-8q12.3. By sequencing the positional candidate neuronal cholinergic receptor α2 subunit gene (CHRNA2), we detected a heterozygous missense mutation, I279N, in the first transmembrane domain that is crucial for receptor function. Whole-cell recordings of transiently transfected HEK293 cells expressing either the mutant or the wild-type receptor showed that the new CHRNA2 mutation markedly increases the receptor sensitivity to acetylcholine, therefore indicating that the nicotinic α2 subunit alteration is the underlying cause. CHRNA2 is the third neuronal cholinergic receptor gene to be associated with familial sleep-related epilepsies. Compared with the CHRNA4 and CHRNB2 mutations reported elsewhere, CHRNA2 mutations cause a more complex and finalized ictal behavior.
AB - Sleep has traditionally been recognized as a precipitating factor for some forms of epilepsy, although differential diagnosis between some seizure types and parasomnias may be difficult. Autosomal dominant frontal lobe epilepsy is characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements and has been associated with mutations of the α4 and β2 subunits of the neuronal nicotinic acetylcholine receptor. We performed a clinical and molecular genetic study of a large pedigree segregating sleep-related epilepsy in which seizures are associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking. We identified a new genetic locus for familial sleep-related focal epilepsy on chromosome 8p12.3-8q12.3. By sequencing the positional candidate neuronal cholinergic receptor α2 subunit gene (CHRNA2), we detected a heterozygous missense mutation, I279N, in the first transmembrane domain that is crucial for receptor function. Whole-cell recordings of transiently transfected HEK293 cells expressing either the mutant or the wild-type receptor showed that the new CHRNA2 mutation markedly increases the receptor sensitivity to acetylcholine, therefore indicating that the nicotinic α2 subunit alteration is the underlying cause. CHRNA2 is the third neuronal cholinergic receptor gene to be associated with familial sleep-related epilepsies. Compared with the CHRNA4 and CHRNB2 mutations reported elsewhere, CHRNA2 mutations cause a more complex and finalized ictal behavior.
UR - http://www.scopus.com/inward/record.url?scp=33746578967&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746578967&partnerID=8YFLogxK
U2 - 10.1086/506459
DO - 10.1086/506459
M3 - Article
C2 - 16826524
AN - SCOPUS:33746578967
VL - 79
SP - 342
EP - 350
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 2
ER -