Rony Cohen1, Lina Basel-Vanagaite2, Hadassah Goldberg-Stern3, Ayelet Halevy3, Avinoam Shuper3, Michal Feingold-Zadok4, Doron M Behar5, Rachel Straussberg6. 1. Department of Pediatric Neurology and Epilepsy Center, Schneider Children's Medical Center of Israel, Petach Tikva 49202, Israel. Electronic address: cohenzr@bezeqint.net. 2. Pediatric Genetic Institute, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Raphael Recanati Genetic Institute, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel; Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 3. Department of Pediatric Neurology and Epilepsy Center, Schneider Children's Medical Center of Israel, Petach Tikva 49202, Israel. 4. Pediatric Genetic Institute, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Raphael Recanati Genetic Institute, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel. 5. Raphael Recanati Genetic Institute, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel; Laboratory of Clinical Biochemistry, Rambam Medical Center, Haifa, Israel. 6. Department of Pediatric Neurology and Epilepsy Center, Schneider Children's Medical Center of Israel, Petach Tikva 49202, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Abstract
AIM: To characterize a new subset of early myoclonic encephalopathy usually associated with metabolic etiologies with a new genetic entity. METHODS: We describe two siblings with early myoclonic encephalopathy born to consanguineous parents of Arab Muslim origin from Israel. We used homozygosity mapping and candidate gene sequencing to reveal the genetic basis of the myoclonic syndrome. RESULTS: We found a rare missense mutation in the gene encoding one of the two mitochondrial glutamate/H symporters, SLC25A22. The phenotype of early myoclonic encephalopathy was first linked to the same mutation in 2005 in patients of the same ethnicity as our family. CONCLUSIONS: Owing to the devastating nature of this encephalopathy, we focus attention on its clinical history, epileptic semiology, distinct electroencephalography features, and genetic basis. We provide the evidence that an integrated diagnostic strategy combining homozygosity mapping with candidate gene sequencing is efficient in consanguineous families with highly heterogeneous autosomal recessive diseases.
AIM: To characterize a new subset of early myoclonic encephalopathy usually associated with metabolic etiologies with a new genetic entity. METHODS: We describe two siblings with early myoclonic encephalopathy born to consanguineous parents of Arab Muslim origin from Israel. We used homozygosity mapping and candidate gene sequencing to reveal the genetic basis of the myoclonic syndrome. RESULTS: We found a rare missense mutation in the gene encoding one of the two mitochondrial glutamate/H symporters, SLC25A22. The phenotype of early myoclonic encephalopathy was first linked to the same mutation in 2005 in patients of the same ethnicity as our family. CONCLUSIONS: Owing to the devastating nature of this encephalopathy, we focus attention on its clinical history, epileptic semiology, distinct electroencephalography features, and genetic basis. We provide the evidence that an integrated diagnostic strategy combining homozygosity mapping with candidate gene sequencing is efficient in consanguineous families with highly heterogeneous autosomal recessive diseases.
Authors: Emma S Reid; Hywel Williams; Glenn Anderson; Malika Benatti; Kling Chong; Chela James; Louise Ocaka; Cheryl Hemingway; Daniel Little; Richard Brown; Alasdair Parker; Simon Holden; Emma Footitt; Shamima Rahman; Paul Gissen; Philippa B Mills; Peter T Clayton Journal: J Inherit Metab Dis Date: 2017-03-02 Impact factor: 4.982
Authors: Atsushi Ishii; Jing-Qiong Kang; Cara C Schornak; Ciria C Hernandez; Wangzhen Shen; Joseph C Watkins; Robert L Macdonald; Shinichi Hirose Journal: J Med Genet Date: 2016-10-27 Impact factor: 6.318