Identification and mutational analysis of candidate genes for juvenile myoclonic epilepsy on 6p11-p12: LRRC1, GCLC, KIAA0057 and CLIC5.
Juvenile myoclonic epilepsy (JME) is one of the most frequent hereditary epilepsies characterized by myoclonic and tonic-clonic convulsions beginning at 8-20 years of age. Genetic studies have revealed four major chromosomal loci on 6p21.3, 6p11-12, 6q24, and 15q14 as candidate regions harboring genes responsible for JME. Previously we reported the region on 6p11-p12 (EJM1), and here we report the identification and mutational analysis of candidate genes for EJM1. One of those is a leucine-rich repeat-containing 1 (LRRC1) gene that is composed of 14 exons and codes for 524 amino acid residues. In Northern analysis, 7 kb transcripts of LRRC1 gene were detected in multiple tissues, most strongly, in heart, lung, and kidney. Mutation analysis of LRRC1 gene in 20 JME patients from ten families revealed one nucleotide substitution that lead to amino acid exchange (c.577 A>G; Ile193Val). This variation, however, did not co-segregate with the disease phenotype. We further performed mutational analyses of CLIC5, KIAA0057 and GCLC genes in or flank to the EJM1 region. These analyses did not provide any evidences that these genes are responsible for the JME phenotype, and suggested that these may not be the EJM1 gene.
Suzuki
Toshimitsu
T
Laboratory for Neurogenetics, Brain Science Institute, The Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Morita
Ryoji
R
Sugimoto
Yoshihisa
Y
Sugawara
Takashi
T
Bai
Dong-Sheng
DS
Alonso
Maria E
ME
Medina
Marco T
MT
Bailey
Julia N
JN
Rasmussen
Astrid
A
Ramos-Peek
Jaime
J
Cordova
Sergio
S
Rubio-Donnadieu
Francisco
F
Ochoa
Adriana
A
Jara-Prado
Aurelio
A
Inazawa
Johji
J
Delgado-Escueta
Antonio V
AV
Yamakawa
Kazuhiro
K
D001483:Base Sequence; D015152:Blotting, Northern; D002874:Chromosome Mapping / Q000379:methods; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020190:Myoclonic Epilepsy, Juvenile / Q000235:genetics*; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
D004247:DNA