Mapping of a gene determining familiar partial epilepsy with variable foci to chromosome 22q11-q12

被引:73
作者
Xiong, L
Labuda, M
Li, DS
Hudson, TJ
Desbiens, R
Patry, G
Verret, S
Langevin, P
Mercho, S
Seni, MH
Scheffer, I
Dubeau, F
Berkovic, SF
Andermann, F
Andermann, E
Pandolfo, M
机构
[1] Univ Montreal, Dept Med, CHU Montreal, Montreal, PQ H3C 3J7, Canada
[2] Montreal Neurol Hosp & Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada
[3] Montreal Gen Hosp, Res Ctr, Montreal, PQ H3G 1A4, Canada
[4] McGill Univ, Dept Human Genet, Montreal, PQ, Canada
[5] Univ Laval, CHU Quebec, Quebec City, PQ, Canada
[6] Univ Melbourne, Dept Med, Austin & Repatriat Med Ctr, Melbourne, Vic, Australia
[7] Royal Childrens Hosp, Dept Neurol, Melbourne, Vic, Australia
[8] Monash Med Ctr, Dept Neurosci, Melbourne, Vic, Australia
关键词
D O I
10.1086/302649
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
We identified two large French-Canadian families segregating a familial partial epilepsy syndrome with variable foci (FPEVF) characterized by mostly nocturnal seizures arising from frontal, temporal, and occasionally occipital epileptic foci. There is no evidence for structural brain damage or permanent neurological dysfunction. The syndrome is inherited as an autosomal dominant trait with incomplete penetrance. We mapped the disease locus to a 3.8-cM interval on chromosome 22q11-q12, between markers D22S1144 and D22S685. Using the most conservative diagnostic scheme, the maximum cumulative LOD score was 6.53 at recombination fraction (theta) 0 with D22S689. The LOD score in the larger family was 5.31 at theta = 0 with the same marker. The two families share an identical linked haplotype for greater than or equal to 10 cM, including the candidate interval, indicating a recent founder effect. A severe phenotype in one of the probands may be caused by homozygosity for the causative mutation, as suggested by extensive homozygosity for the linked haplotype and a bilineal family history of epilepsy. An Australian family with a similar phenotype was not found to link to chromosome 22, indicating genetic heterogeneity of FPEVF.
引用
收藏
页码:1698 / 1710
页数:13
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