Evaluation of a putative major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q14.
Juvenile myoclonic epilepsy (JME) is a genetically determined common subtype of idiopathic generalized epilepsy (IGE). Significant evidence for linkage has been reported for a susceptibility locus for JME in the chromosomal region 15q14 that harbors the gene encoding the alpha7 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA7). The present study was designed to test the earlier linkage finding and to explore whether this susceptibility locus is involved in the epileptogenesis of a broader spectrum of IGE syndromes. Multipoint parametric and nonparametric linkage analyses with seven microsatellite polymorphisms encompassing the region of the CHRNA7 gene were performed using two diagnostic schemes of JME-related traits in two groups of multiplex families ascertained through probands with either JME (n = 27) or idiopathic absence epilepsy (n = 30). The present linkage study failed to replicate evidence for a major susceptibility locus for JME in the region encompassing the CHRNA7 gene. In addition, we found no hint in favor of linkage to 15q14 under the broad diagnostic scheme in any of the sets of families. If genetic variation in this region confers susceptibility to JME, then its effect size might be too small or its occurrence too rare to be detected in the investigated families.
Sander
T
T
Department of Neurology, University Hospital Rudolf Virchow, Humboldt University of Berlin, Germany. Sanderth@aol.com
Schulz
H
H
Vieira-Saeker
A M
AM
Bianchi
A
A
Sailer
U
U
Bauer
G
G
Scaramelli
A
A
Wienker
T F
TF
Saar
K
K
Reis
A
A
Janz
D
D
Epplen
J T
JT
Riess
O
O
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002884:Chromosomes, Human, Pair 15; D004831:Epilepsies, Myoclonic / Q000175:diagnosis / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D018895:Microsatellite Repeats; D015999:Multivariate Analysis; D011978:Receptors, Nicotinic / Q000235:genetics; D017422:Sequence Analysis, DNA; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor