Document Details
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Document Type |
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Thesis |
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Document Title |
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GENETIC ASSESSMENT OF SUDDEN CARDIAC DEATH MUTATIONS IN SAMPLES FROM SAUDI ARABIA RESIDENTS التقييم الوراثي لبعض الطفرات المرتبطة بحالات الموت المفاجئ في عينة من قاطني المملكة العربية السعودية |
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Subject |
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Faculty of Sciences |
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Document Language |
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Arabic |
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Abstract |
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Sudden cardiac death (SCD) refers to (death resulting from cardiac problem and occurred shortly after the onset of symptoms). Coronary artery disease (CAD) is the main cause of SCD in adults. In contrast, most of children and adolescents that die suddenly have some form of inherited heart disease of which inherited arrhythmia syndromes are most common followed by dilated cardiomyopathy, structural heat defects and others. In some cases SCD is unexplained. SCD is prevalent worldwide and very common in Saudi Arabia due to the high percentage of consanguinity, which ranges between 34% to 80% (depending on the province). The objective of this study is to detect the underlying genetic pathogenic mutations, determine whether they are known or novel, identify founder variations in genes involved in arrhythmia syndromes, and discover potential candidate genes responsible for the unexplained sudden death. A total of twenty families who presented to the cardiac or genetic clinic with a family history of SCD were recruited. Sanger sequencing was done to check the presence of pathogenic mutations in the most common genes causing arrhythmia syndrome. Whole exome sequencing (WES) was done for one big family with a history of unexplained sudden death in many children and no mutation detected in the most common genes causing arrhythmia syndrome. We identified different missense, nonsense, and splice site mutations in the KCNQ1 gene in seventeen families. Of these, eight families were found to have Autosomal Recessive Long QT syndrome, type 1 (AR LQT1), seven families were found to have Jervel-Lange Nelson syndrome (JLNS), and two families were found to have Autosomal Dominant Long QT syndrome, type 1. We identified KCNH2 mutations in two families and that lead to a diagnosis of Long QT syndrome, type 2. Founder and novel mutations were identified in the previous two genes. In addition, WES identified a novel pathogenic mutation in the CYB5R1 gene. We suspect this caused sudden death in many children in this family. In conclusion, among the various forms of familial arrhythmias, Long QT syndrome is more predominant in Saudi Arabia, and out of different forms of LQTs, LQT1 caused by mutations in the KCNQ1 gene is more common with about 85% of patients carry mutations in this gene, and 10% have mutations in the KCNH2 gene which cause LQT2. Recessive forms of Long QT syndrome type1 have been widely spread in Saudi Arabia. Due to the homozygous mutations, clinical phenotypes were particularly severe in these families. These genetic and phenotypic observations stem from the high rate of consanguineous marriage in Saudi Arabia. |
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Supervisor |
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Dr. Sherif Edris |
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Thesis Type |
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Doctorate Thesis |
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Publishing Year |
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1439 AH
2018 AD |
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Co-Supervisor |
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Prof. Jumana Al-Aama |
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Added Date |
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Tuesday, June 5, 2018 |
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Researchers
| امنه يوسف بدير | Bdeir, Amnah Yousef | Researcher | Doctorate | |
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