دورية أكاديمية
Exome-based analysis of cardiac arrhythmia, respiratory control, and epilepsy genes in sudden unexpected death in epilepsy.
| العنوان: | Exome-based analysis of cardiac arrhythmia, respiratory control, and epilepsy genes in sudden unexpected death in epilepsy. |
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| المؤلفون: | Bagnall RD; Agnes Ginges Center for Molecular Cardiology, Centenary Institute, Sydney, Australia.; Sydney Medical School, University of Sydney, Sydney, Australia., Crompton DE; Neurology Department, Northern Health, Melbourne, Australia.; Epilepsy Research Center, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia., Petrovski S; Epilepsy Research Center, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia.; Institute for Genomic Medicine, Columbia University, New York, NY., Lam L; Agnes Ginges Center for Molecular Cardiology, Centenary Institute, Sydney, Australia.; Sydney Medical School, University of Sydney, Sydney, Australia., Cutmore C; Agnes Ginges Center for Molecular Cardiology, Centenary Institute, Sydney, Australia.; Sydney Medical School, University of Sydney, Sydney, Australia., Garry SI; Epilepsy Research Center, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia., Sadleir LG; Department of Pediatrics and Child Health, School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand., Dibbens LM; Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia., Cairns A; Neurosciences Department, Lady Cilento Children's Hospital, Brisbane, Australia., Kivity S; Epilepsy Unit, Schneider Children's Medical Center of Israel, Petach Tikvah, Israel., Afawi Z; Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel., Regan BM; Epilepsy Research Center, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia., Duflou J; Sydney Medical School, University of Sydney, Sydney, Australia.; Department of Forensic Medicine, Sydney, Australia., Berkovic SF; Epilepsy Research Center, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia., Scheffer IE; Epilepsy Research Center, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia.; Department of Neurology, The Royal Children's Hospital, Parkville, Melbourne, Victoria, Australia.; Florey Institute of Neurosciences and Mental Health, Melbourne, Australia.; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Australia., Semsarian C; Agnes Ginges Center for Molecular Cardiology, Centenary Institute, Sydney, Australia.; Sydney Medical School, University of Sydney, Sydney, Australia.; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia. |
| المصدر: | Annals of neurology [Ann Neurol] 2016 Apr; Vol. 79 (4), pp. 522-34. Date of Electronic Publication: 2016 Feb 02. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Liss Country of Publication: United States NLM ID: 7707449 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1531-8249 (Electronic) Linking ISSN: 03645134 NLM ISO Abbreviation: Ann Neurol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York, NY : Wiley-Liss Original Publication: Boston, Little, Brown. |
| مواضيع طبية MeSH: | Exome*, Arrhythmias, Cardiac/*genetics , Death, Sudden/*etiology , Epilepsy/*genetics , Respiration Disorders/*genetics, Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Genes, Dominant ; Humans ; Infant ; Long QT Syndrome/genetics ; Male ; Middle Aged ; Mutation ; Young Adult |
| مستخلص: | Objective: The leading cause of epilepsy-related premature mortality is sudden unexpected death in epilepsy (SUDEP). The cause of SUDEP remains unknown. To search for genetic risk factors in SUDEP cases, we performed an exome-based analysis of rare variants. Methods: Demographic and clinical information of 61 SUDEP cases were collected. Exome sequencing and rare variant collapsing analysis with 2,936 control exomes were performed to test for genes enriched with damaging variants. Additionally, cardiac arrhythmia, respiratory control, and epilepsy genes were screened for variants with frequency of <0.1% and predicted to be pathogenic with multiple in silico tools. Results: The 61 SUDEP cases were categorized as definite SUDEP (n = 54), probable SUDEP (n = 5), and definite SUDEP plus (n = 2). We identified de novo mutations, previously reported pathogenic mutations, or candidate pathogenic variants in 28 of 61 (46%) cases. Four SUDEP cases (7%) had mutations in common genes responsible for the cardiac arrhythmia disease, long QT syndrome (LQTS). Nine cases (15%) had candidate pathogenic variants in dominant cardiac arrhythmia genes. Fifteen cases (25%) had mutations or candidate pathogenic variants in dominant epilepsy genes. No gene reached genome-wide significance with rare variant collapsing analysis; however, DEPDC5 (p = 0.00015) and KCNH2 (p = 0.0037) were among the top 30 genes, genome-wide. Interpretation: A sizeable proportion of SUDEP cases have clinically relevant mutations in cardiac arrhythmia and epilepsy genes. In cases with an LQTS gene mutation, SUDEP may occur as a result of a predictable and preventable cause. Understanding the genetic basis of SUDEP may inform cascade testing of at-risk family members. (© 2016 American Neurological Association.) |
| تواريخ الأحداث: | Date Created: 20151226 Date Completed: 20160906 Latest Revision: 20220408 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1002/ana.24596 |
| PMID: | 26704558 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1531-8249 |
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| DOI: | 10.1002/ana.24596 |