title: Novel mutations in Myoclonin1/EFHC1 in sporadic and familial juvenile myoclonic epilepsy.
abstract: 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.
authors.affiliation: Neurology Training Program, National Autonomous University of Honduras, Tegucigalpa, Honduras.
authors.forename: M T
authors.initials: MT
authors.lastname: Medina
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: M E
authors.initials: ME
authors.lastname: Alonso
authors.forename: R M
authors.initials: RM
authors.lastname: Durón
authors.forename: I E
authors.initials: IE
authors.lastname: Martínez-Juárez
authors.forename: J N
authors.initials: JN
authors.lastname: Bailey
authors.forename: D
authors.initials: D
authors.lastname: Bai
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: I
authors.initials: I
authors.lastname: Yoshimura
authors.forename: S
authors.initials: S
authors.lastname: Kaneko
authors.forename: M C
authors.initials: MC
authors.lastname: Montoya
authors.forename: A
authors.initials: A
authors.lastname: Ochoa
authors.forename: A Jara
authors.initials: AJ
authors.lastname: Prado
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: J
authors.initials: J
authors.lastname: Machado-Salas
authors.forename: S
authors.initials: S
authors.lastname: Fujimoto
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: S
authors.initials: S
authors.lastname: Hamano
authors.forename: K
authors.initials: K
authors.lastname: Sugita
authors.forename: Y
authors.initials: Y
authors.lastname: Ueda
authors.forename: M
authors.initials: M
authors.lastname: Osawa
authors.forename: H
authors.initials: H
authors.lastname: Oguni
authors.forename: F
authors.initials: F
authors.lastname: Rubio-Donnadieu
authors.forename: K
authors.initials: K
authors.lastname: Yamakawa
authors.forename: A V
authors.initials: AV
authors.lastname: Delgado-Escueta
mesh_terms: 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
chemical_list: D000090007:CLC-2 Chloride Channels; D002135:Calcium-Binding Proteins; D018118:Chloride Channels; C489648:EFHC1 protein, human; C546240:GABRA1 protein, human; D011963:Receptors, GABA-A