Exclusion of linkage of nine neuronal nicotinic acetylcholine receptor subunit genes expressed in brain in autosomal dominant nocturnal frontal lobe epilepsy in four unrelated families.
Members of the ligand-gated neuronal nicotinic acetylcholine receptor (nAChR) gene family ( CHRNA4 and CHRNB2, coding for the alpha4 and beta2 subunits, respectively) are involved in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). However, ADNFLE is genetically heterogeneous and mutations in CHRNA4 and CHRNB2 account for only a minority of ADNFLE cases. Additional nAChR subunits expressed in the brain are candidates for this epilepsy. The involvement of all genes coding for brain-expressed nAChR subunits, with known chromosome localization ( CHRNB2, 1q21; CHRNA2, 8p21; CHRNA6, CHRNB3, 8p11.2; CHRNA7, 15q14; CHRNA5/A3/B4, 15q24 and CHRNA4, 20q13.2) was investigated in four unrelated ADNFLE Italian families for at least three generations. Families were selected on the basis of anamnestic and videopolysomnographic analyses. Individuals were typed for polymorphic markers located in the above mentioned chromosome regions. Linkage and mutation analyses were performed. In none of the families was linkage between ADNFLE and the analysed chromosome regions detected. These findings support the hypothesis that genes different from those coding for alpha2-7 and beta2-4 neuronal nAChR subunits could be responsible for ADNFLE.
Department of Biology and Genetics for Medical Sciences, University of Milan, Via Viotti 3/5, 20133 Milan, Italy.
Maria Teresa
MT
Bonati
Romina
R
Combi
Rosanna
R
Asselta
Stefano
S
Duga
Massimo
M
Malcovati
Alessandro
A
Oldani
Marco
M
Zucconi
Luigi
L
Ferini-Strambi
Leda
L
Dalprà
Maria Luisa
ML
Tenchini
D001921:Brain / Q000502:physiology; D017034:Epilepsy, Frontal Lobe / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D011978:Receptors, Nicotinic / Q000235:genetics*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C447159:CHRNB4 protein, human; C579167:Chrna7 protein, human