Autosomal dominant nocturnal frontal-lobe epilepsy: Genetic heterogeneity and evidence for a second locus at 15q24

被引:163
作者
Phillips, HA
Scheffer, IE
Crossland, KM
Bhatia, KP
Fish, DR
Marsden, CD
Howell, SJL
Stephenson, JBP
Tolmie, J
Plazzi, G
Eeg-Olofsson, O
Singh, R
Lopes-Cendes, I
Andermann, E
Andermann, F
Berkovic, SF
Mulley, JC
机构
[1] Womens & Childrens Hosp, Dept Cytogenet & Mol Genet, Ctr Med Genet, Adelaide, SA 5006, Australia
[2] Univ Melbourne, Austin & Repatriat Med Ctr, Dept Med Neurol, Heidelberg, Vic, Australia
[3] Neurol Inst, London, England
[4] Royal Hallamshire Hosp, Sheffield S10 2JF, S Yorkshire, England
[5] Royal Hosp Sick Children, Glasgow G3 8SJ, Lanark, Scotland
[6] Univ Bologna, Inst Clin Neurol, Bologna, Italy
[7] Univ Uppsala, Childrens Hosp, Child Neurol Unit, Uppsala, Sweden
[8] Montreal Neurol Hosp & Inst, Montreal, PQ H3A 2B4, Canada
[9] Univ Adelaide, Dept Genet, Adelaide, SA, Australia
基金
英国医学研究理事会;
关键词
D O I
10.1086/302047
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Autosomal dominant nocturnal frontal-lobe epilepsy (ADNFLE) is a recently identified partial epilepsy in which two different mutations have been described in the alpha 4 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4). An additional seven families are presented in which ADNFLE is unlinked to the CHRNA4 region on chromosome 20q13.2. Seven additional sporadic cases showed no evidence of defective CHRNA4. One of the families showed evidence of linkage to 15q24, close to the CHRNA3/CHRNA5/CHRNB4 cluster (maximum LOD score of 3.01 with D15S152). Recombination between ADNFLE and CHRNA4, linkage to 15q24 in one family, and exclusion from 15q24 and 20q13.2 in others demonstrate genetic heterogeneity with at least three different genes for ADNFLE. The CHRNA4 gene and the two known CHRNA4 mutations are responsible for only a minority of ADNFLE. Although the ADNFLE phenotype is clinically homogeneous, there appear to be a variety of molecular defects responsible for this disorder, which will provide a challenge to the understanding of the basic mechanism of epileptogenesis.
引用
收藏
页码:1108 / 1116
页数:9
相关论文
共 40 条
[1]  
Berkovic Samuel F., 1995, Epilepsia, V36, P147
[2]   Epilepsies with single gene inheritance [J].
Berkovic, SF ;
Scheffer, IE .
BRAIN & DEVELOPMENT, 1997, 19 (01) :13-18
[3]   A potassium channel mutation in neonatal human epilepsy [J].
Biervert, C ;
Schroeder, BC ;
Kubisch, C ;
Berkovic, SF ;
Propping, P ;
Jentsch, TJ ;
Steinlein, OK .
SCIENCE, 1998, 279 (5349) :403-406
[4]  
BOULTER J, 1990, J BIOL CHEM, V265, P4472
[5]   A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family [J].
Charlier, C ;
Singh, NA ;
Ryan, SG ;
Lewis, TB ;
Reus, BE ;
Leach, RJ ;
Leppert, M .
NATURE GENETICS, 1998, 18 (01) :53-55
[6]   A comprehensive genetic map of the human genome based on 5,264 microsatellites [J].
Dib, C ;
Faure, S ;
Fizames, C ;
Samson, D ;
Drouot, N ;
Vignal, A ;
Millasseau, P ;
Marc, S ;
Hazan, J ;
Seboun, E ;
Lathrop, M ;
Gyapay, G ;
Morissette, J ;
Weissenbach, J .
NATURE, 1996, 380 (6570) :152-154
[7]   Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q [J].
Elmslie, FV ;
Rees, M ;
Williamson, MP ;
Kerr, M ;
Kjeldsen, MJ ;
Pang, KA ;
Sundqvist, A ;
Friis, ML ;
Chadwick, D ;
Richens, A ;
Covanis, A ;
Santos, M ;
Arzimanoglou, A ;
Panayiotopoulos, CP ;
Curtis, D ;
Whitehouse, WP ;
Gardiner, RM .
HUMAN MOLECULAR GENETICS, 1997, 6 (08) :1329-1334
[8]   MAPPING OF MULTIPLE SUBUNITS OF THE NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTOR TO CHROMOSOME-15 IN MAN AND CHROMOSOME-9 IN MOUSE [J].
ENG, CM ;
KOZAK, CA ;
BEAUDET, AL ;
ZOGHBI, HY .
GENOMICS, 1991, 9 (02) :278-282
[9]   New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome [J].
Engel, AG ;
Ohno, K ;
Milone, M ;
Wang, HL ;
Nakano, S ;
Bouzat, C ;
Pruitt, JN ;
Hutchinson, DO ;
Brengman, JM ;
Bren, N ;
Sieb, JP ;
Sine, SM .
HUMAN MOLECULAR GENETICS, 1996, 5 (09) :1217-1227
[10]   Linkage mapping of benign familial infantile convulsions (BFIC) to chromosome 19q [J].
Guipponi, M ;
Rivier, F ;
Vigevano, F ;
Beck, C ;
Crespel, A ;
Echenne, B ;
Lucchini, P ;
Sebastianelli, R ;
BaldyMoulinier, M ;
Malafosse, A .
HUMAN MOLECULAR GENETICS, 1997, 6 (03) :473-477