Clinical and genetic analysis of a large pedigree with juvenile myoclonic epilepsy.
Juvenile myoclonic epilepsy is a common type of idiopathic generalized epilepsy characterized by myoclonic, generalized tonic-clonic, and in 30% of patients, absence seizures. We studied a three-generation pedigree of 33 members, 10 of whom were clinically affected with juvenile myoclonic epilepsy or presented with subclinical electroencephalographic (EEG) 3.5- to 6.0-Hz diffuse polyspike-wave or spike-wave complexes. Juvenile myoclonic epilepsy and the EEG trait segregated as an autosomal dominant trait with 70% penetrance. Linkage analysis using this model showed significant linkage to four microsatellite markers centromeric to human leukocyte antigen (HLA) in chromosome 6p. Maximum lod scores of 3.43 at theta(m=f)=0.00 for D6S272, D6S466, D6S257, and D6S402 were obtained. Recombinant events in 2 affected members defined the gene region to a 43-cM interval flanked by D6S258 (HLA region) and D6S313 (centromere). Our results in this large family provide evidence that a gene responsible for juvenile myoclonic epilepsy and the subclinical, 3.5- to 6.0-Hz, polyspike-wave or spike-wave EEG pattern is located in chromosome 6p.
Serratosa
J M
JM
California Comprehensive Epilepsy Program, University of California, Los Angeles, 90073, USA.
Delgado-Escueta
A V
AV
Medina
M T
MT
Zhang
Q
Q
Iranmanesh
R
R
Sparkes
R S
RS
D000293:Adolescent; D000328:Adult; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010375:Pedigree; D011995:Recombination, Genetic