TY - JOUR
T1 - No evidence for a susceptibility locus for idiopathic generalized epilepsy on chromosome 18q21.1
AU - Sander, Thomas
AU - Windemuth, Christine
AU - Schulz, Herbert
AU - Saar, Kathrin
AU - Gennaro, Elena
AU - Bianchi, Amedeo
AU - Zara, Federico
AU - Bulteau, Christine
AU - Kaminska, Anna
AU - Ville, Dorothée
AU - Cieuta, Cécile
AU - Prud'homme, Jean François
AU - Dulac, Olivier
AU - Bate, Louise
AU - Gardiner, R. Mark
AU - De Haan, Gerrit Jan
AU - Janssen, Guus A M A J
AU - Witte, Jorine
AU - Halley, Dicky J J
AU - Lindhout, Dick
AU - Wienker, Thomas F.
AU - Janz, Dieter
PY - 2002/8/8
Y1 - 2002/8/8
N2 - 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 θm=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, nonparametric 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.
AB - 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 θm=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, nonparametric 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.
KW - Chromosome 18
KW - Genetics
KW - Idiopathic generalized epilepsy
KW - Linkage
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U2 - 10.1002/ajmg.10645
DO - 10.1002/ajmg.10645
M3 - Article
C2 - 12210286
AN - SCOPUS:0037044006
VL - 114
SP - 673
EP - 678
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
SN - 1552-4841
IS - 6
ER -