Novel mutations in Myoclonin1/EFHC1 in sporadic and familial juvenile myoclonic epilepsy.
BACKGROUND
Juvenile myoclonic epilepsy (JME) accounts for 3 to 12% of all epilepsies. In 2004, the GENESS Consortium demonstrated four missense mutations in Myoclonin1/EFHC1 of chromosome 6p12.1 segregating in 20% of Hispanic families with JME.


OBJECTIVE
To examine what percentage of consecutive JME clinic cases have mutations in Myoclonin1/EFHC1.


METHODS
We screened 44 consecutive patients from Mexico and Honduras and 67 patients from Japan using heteroduplex analysis and direct sequencing.


RESULTS
We found five novel mutations in transcripts A and B of Myoclonin1/EFHC1. Two novel heterozygous missense mutations (c.755C>A and c.1523C>G) in transcript A occurred in both a singleton from Mexico and another singleton from Japan. A deletion/frameshift (C.789del.AV264fsx280) in transcript B was present in a mother and daughter from Mexico. A nonsense mutation (c.829C>T) in transcript B segregated in four clinically and seven epileptiform-EEG affected members of a large Honduran family. The same nonsense mutation (c.829C>T) occurred as a de novo mutation in a sporadic case. Finally, we found a three-base deletion (-364--362del.GAT) in the promoter region in a family from Japan.


CONCLUSIONS
Nine percent of consecutive juvenile myoclonic epilepsy cases from Mexico and Honduras clinics and 3% of clinic patients from Japan carry mutations in Myoclonin1/EFCH1. These results represent the highest number and percentage of mutations found for a juvenile myoclonic epilepsy causing gene of any population group.
Medina
M T
MT
Neurology Training Program, National Autonomous University of Honduras, Tegucigalpa, Honduras.
Suzuki
T
T
Alonso
M E
ME
Durón
R M
RM
Martínez-Juárez
I E
IE
Bailey
J N
JN
Bai
D
D
Inoue
Y
Y
Yoshimura
I
I
Kaneko
S
S
Montoya
M C
MC
Ochoa
A
A
Prado
A Jara
AJ
Tanaka
M
M
Machado-Salas
J
J
Fujimoto
S
S
Ito
M
M
Hamano
S
S
Sugita
K
K
Ueda
Y
Y
Osawa
M
M
Oguni
H
H
Rubio-Donnadieu
F
F
Yamakawa
K
K
Delgado-Escueta
A V
AV
D000090007:CLC-2 Chloride Channels; D002135:Calcium-Binding Proteins / Q000235:genetics*; D018118:Chloride Channels / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D005838:Genotype; D006721:Honduras / Q000453:epidemiology; D006801:Humans; D007564:Japan; D008297:Male; D008800:Mexico / Q000453:epidemiology; D009154:Mutation; D020190:Myoclonic Epilepsy, Juvenile / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011963:Receptors, GABA-A / Q000235:genetics
D000090007:CLC-2 Chloride Channels; D002135:Calcium-Binding Proteins; D018118:Chloride Channels; C489648:EFHC1 protein, human; C546240:GABRA1 protein, human; D011963:Receptors, GABA-A