title: DNA variants in coding region of EFHC1: SNPs do not associate with juvenile myoclonic epilepsy.
abstract: OBJECTIVE
  Juvenile myoclonic epilepsy (JME) accounts for 3 to 12% of all epilepsies. In 2004, we identified a mutation-harboring Mendelian gene that encodes a protein with one EF-hand motif (EFHC1) in chromosome 6p12. We observed one doubly heterozygous and three heterozygous missense mutations in EFHC1 segregating as an autosomal dominant gene with 21 affected members of six Hispanic JME families from California and Mexico. In 2006, similar and three novel missense mutations were reported in sporadic and familial Caucasian JME from Italy and Austria. In this study, we asked if coding single nucleotide polymorphisms (SNPs) of EFHC1 also contribute as susceptibility alleles to JME with complex genetics.
  
  
  METHODS
  We screened using denaturing high-performance liquid chromatography (DHPLC) and then directly sequenced the 11 exons of EFHC1 in 130 unrelated JME probands, their 352 family members, and seven exons of EFHC1 in 400-614 ethnically matched controls. We carried out case-control association studies between 124 unrelated Hispanic JME probands and 552-614 ethnically matched controls using four SNPs, rs3804506, rs3804505, rs1266787, and rs17851770. We also performed family-based association on SNPs rs3804506 and rs3804505 in 84 complete JME families using the Family-Based Association Test (FBAT) program.
  
  
  RESULTS
  We found no statistically significant differences between JME probands and controls in case-control association and no genetic transmission disequilibria in family-based association for the tested SNPs. In addition, we identified four new DNA variants in the coding region of EFHC1.
  
  
  CONCLUSIONS
  The four coding SNPs, rs3804506, rs3804505, rs1266787, and rs17851770, of EFHC1 may not be susceptibility alleles for JME.
authors.affiliation: Epilepsy Genetics/Genomics Lab, CEP, UCLA & VA GLAHS, Los Angeles, California 90073, USA.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Bai
authors.forename: Julia N
authors.initials: JN
authors.lastname: Bailey
authors.forename: Reyna M
authors.initials: RM
authors.lastname: Durón
authors.forename: María E
authors.initials: ME
authors.lastname: Alonso
authors.forename: Marco T
authors.initials: MT
authors.lastname: Medina
authors.forename: Iris E
authors.initials: IE
authors.lastname: Martínez-Juárez
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Jesús
authors.initials: J
authors.lastname: Machado-Salas
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ramos-Ramírez
authors.forename: Miyabi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Ramón H Castro
authors.initials: RH
authors.lastname: Ortega
authors.forename: Minerva
authors.initials: M
authors.lastname: López-Ruiz
authors.forename: Astrid
authors.initials: A
authors.lastname: Rasmussen
authors.forename: Adriana
authors.initials: A
authors.lastname: Ochoa
authors.forename: Aurelio
authors.initials: A
authors.lastname: Jara-Prado
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamakawa
authors.forename: Antonio V
authors.initials: AV
authors.lastname: Delgado-Escueta
mesh_terms: D002135:Calcium-Binding Proteins / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020190:Myoclonic Epilepsy, Juvenile / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D002135:Calcium-Binding Proteins; C489648:EFHC1 protein, human