No evidence for a susceptibility locus for idiopathic generalized epilepsy on chromosome 18q21.1.
A recent genome-wide scan showed strong evidence for a major locus for common syndromes of idiopathic generalized epilepsy (IGE) at the marker D18S474 on chromosome 18q21.1 (LOD score 4.5/5.2 multipoint/two-point). The present replication study tested the presence of an IGE locus in the chromosomal region 18q21.1. Our linkage study included 130 multiplex families of probands with common IGE syndromes. Eleven microsatellite polymorphisms encompassing a candidate region of 30 cM on either side of the marker D18S474 were genotyped. The two-point homogeneity LOD score for D18S474 showed strong evidence against linkage at the original linkage peak (Z = -18.86 at theta(m = f) = 0.05), assuming a recessive mode of inheritance with 50% penetrance. Multipoint parametric heterogeneity LOD scores < -2 were obtained along the candidate region when proportions of linked families greater than 35% were assumed under recessive inheritance. Furthermore, non-parametric multipoint linkage analyses showed no hint of linkage throughout the candidate region (P > 0.19). Accordingly, we failed to support evidence for a major IGE locus in the chromosomal region 18p11-18q23. If there is a susceptibility locus for IGE in this region then the size of the effect or the proportion of linked families is too small to detect linkage in the investigated family sample.
Sander
Thomas
T
Epilepsy Genetics Group, Department of Neurology, University Clinic Charité, Humboldt University of Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Sanderth@aol.com
Windemuth
Christine
C
Schulz
Herbert
H
Saar
Kathrin
K
Gennaro
Elena
E
Bianchi
Amedeo
A
Zara
Federico
F
Bulteau
Christine
C
Kaminska
Anna
A
Ville
Dorothée
D
Cieuta
Cécile
C
Prud'homme
Jean-François
JF
Dulac
Olivier
O
Bate
Louise
L
Gardiner
R Mark
RM
de Haan
Gerrit-Jan
GJ
Janssen
Guus A M A J
GA
Witte
Jorine
J
Halley
Dicky J J
DJ
Lindhout
Dick
D
Wienker
Thomas F
TF
Janz
Dieter
D
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D004198:Disease Susceptibility; D004831:Epilepsies, Myoclonic / Q000235:genetics; D004829:Epilepsy, Generalized / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008957:Models, Genetic; D009679:Nuclear Family; D011110:Polymorphism, Genetic
D005819:Genetic Markers