Exploration of a putative susceptibility locus for idiopathic generalized epilepsy on chromosome 8p12.
OBJECTIVE
A recent genome-wide scan revealed a major susceptibility locus for idiopathic generalized epilepsies (IGEs) in the chromosomal region 8p12 in 32 IGE families without members with juvenile myoclonic epilepsy (JME). This study explored the presence of an IGE locus in the chromosomal region 8p12.


METHODS
Our study included 176 multiplex families of probands with common IGE syndromes. Parametric and nonparametric multipoint linkage analyses were carried out between the IGE trait and six microsatellite polymorphisms encompassing the putative susceptibility locus. To explore the associated phenotype-genotype relation, two distinct subgroups of families were selected by the presence (n = 64) or absence (n = 112) of a family member with JME. To adjust the phenotypic spectrum toward adolescent-onset IGEs, a third subgroup of 28 families without JME was chosen through an IGE proband with seizure onset at age 10-20 years.


RESULTS
Parametric and nonparametric multipoint linkage analyses provided no evidence for linkage between IGE and markers encompassing the putative IGE locus in the chromosomal region 8p12. Furthermore, we found no hint of linkage along the candidate region in any of the three family subgroups.


CONCLUSIONS
We failed to provide evidence for a major IGE locus in the chromosomal region 8p12. On the contrary, these parametric linkage results provide strong evidence against linkage across the candidate region under a broad range of genetic models. If there is a susceptibility locus for IGE in the chromosomal region 8p12, 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
Epilepsie Genetik Gruppe, Neurologische Klinik, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, Germany. Sanderth@aol.com
Windemuth
Christine
C
Schulz
Herbert
H
Saar
Kathrin
K
Gennaro
Elena
E
Riggio
Concetta
C
Bianchi
Amedeo
A
Zara
Federico
F
Rudolf
Gabrielle
G
Picard
Fabienne
F
Bulteau
Christine
C
Kaminska
Anna
A
Cieuta
Cécile
C
Prud'homme
Jean-François
JF
Dulac
Olivier
O
Bate
Louise
L
Robinson
Robert
R
Gardiner
R Mark
RM
Covanis
Athanasios
A
de Haan
Gerrit-Jan
GJ
Janssen
Guus A M A J
GA
van Erp
M Gerard
MG
Boezeman
Eduard H J F
EH
Lindhout
Dick
D
Heils
Armin
A
Nürnberg
Peter
P
Janz
Diéter
D
D000328:Adult; D000483:Alleles; D002648:Child; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D018900:Dinucleotide Repeats; D004832:Epilepsy, Absence / Q000235:genetics; D004829:Epilepsy, Generalized / Q000235:genetics*; D004830:Epilepsy, Tonic-Clonic / Q000235:genetics; D005060:Europe; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000145:classification*; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D020190:Myoclonic Epilepsy, Juvenile / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D013577:Syndrome
D005819:Genetic Markers