PURPOSE: 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. CONCLUSION: The four coding SNPs, rs3804506, rs3804505, rs1266787, and rs17851770, of EFHC1 may not be susceptibility alleles for JME.
PURPOSE: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. CONCLUSION: The four coding SNPs, rs3804506, rs3804505, rs1266787, and rs17851770, of EFHC1 may not be susceptibility alleles for JME.
Authors: Dalila Pinto; Sandrien Louwaars; Birgit Westland; Linda Volkers; Gerrit-Jan de Haan; Dorothée G A Kasteleijn-Nolst Trenité; Dick Lindhout; Bobby P C Koeleman Journal: Epilepsia Date: 2006-10 Impact factor: 5.864
Authors: Shaochun Ma; Marcia A Blair; Bassel Abou-Khalil; Andre H Lagrange; Christina A Gurnett; Peter Hedera Journal: Epilepsy Res Date: 2006-07-12 Impact factor: 3.045
Authors: Dongsheng Bai; Maria E Alonso; Marco T Medina; Julia N Bailey; Ryoji Morita; Sergio Cordova; Astrid Rasmussen; Jaime Ramos-Peek; Adriana Ochoa; Aurelio Jara; Francisco R Donnadieu; Gilbert Cadena; Kazuhiro Yamakawa; Antonio V Delgado-Escueta Journal: Am J Med Genet Date: 2002-12-01
Authors: E Stogmann; P Lichtner; C Baumgartner; S Bonelli; E Assem-Hilger; F Leutmezer; M Schmied; C Hotzy; T M Strom; T Meitinger; F Zimprich; A Zimprich Journal: Neurology Date: 2006-12-12 Impact factor: 9.910
Authors: Karsten Haug; Maike Warnstedt; Alexi K Alekov; Thomas Sander; Alfredo Ramírez; Barbara Poser; Snezana Maljevic; Simon Hebeisen; Christian Kubisch; Johannes Rebstock; Steve Horvath; Kerstin Hallmann; Joern S Dullinger; Birgit Rau; Fritz Haverkamp; Stefan Beyenburg; Herbert Schulz; Dieter Janz; Bernd Giese; Gerhard Müller-Newen; Peter Propping; Christian E Elger; Christoph Fahlke; Holger Lerche; Armin Heils Journal: Nat Genet Date: 2003-03-03 Impact factor: 38.330
Authors: A W Liu; A V Delgado-Escueta; J M Serratosa; M E Alonso; M T Medina; M N Gee; S Cordova; H Z Zhao; J M Spellman; J R Peek Journal: Am J Hum Genet Date: 1995-08 Impact factor: 11.025
Authors: Anne Hempelmann; Kirsten P Taylor; Armin Heils; Susanne Lorenz; Jean-Francois Prud'homme; Rima Nabbout; Olivier Dulac; Gabrielle Rudolf; Federico Zara; Amedeo Bianchi; Robert Robinson; R Mark Gardiner; Athanasios Covanis; Dick Lindhout; Ulrich Stephani; Christian E Elger; Yvonne G Weber; Holger Lerche; Peter Nürnberg; Katherine L Kron; Ingrid E Scheffer; John C Mulley; Samuel F Berkovic; Thomas Sander Journal: Epilepsia Date: 2006-10 Impact factor: 5.864
Authors: Julia N Bailey; Christopher Patterson; Laurence de Nijs; Reyna M Durón; Viet-Huong Nguyen; Miyabi Tanaka; Marco T Medina; Aurelio Jara-Prado; Iris E Martínez-Juárez; Adriana Ochoa; Yolli Molina; Toshimitsu Suzuki; María E Alonso; Jenny E Wight; Yu-Chen Lin; Laura Guilhoto; Elza Marcia Targas Yacubian; Jesús Machado-Salas; Andrea Daga; Kazuhiro Yamakawa; Thierry M Grisar; Bernard Lakaye; Antonio V Delgado-Escueta Journal: Genet Med Date: 2016-07-28 Impact factor: 8.822