Document Details

Document Type : Thesis 
Document Title :
Identification of Molecular Cause of Multiple Sudden Cardiac Deaths (SCD) in a Saudi Family Using Clinical Whole Exome Sequencing
التعرف على المسبب الجزيئي للوفيات القلبية المفاجئة لعائلة سعودية بإستخدام تقنية فحص تسلسل الأكسونات بالكامل
 
Subject : Faculty of medicine 
Document Language : Arabic 
Abstract : Sudden cardiac death (SCD) in patients with Dilated cardiomyopathy (DCM; OMIM 115200) is a major cause of mortality among children and adolescents. Whereas, in most adult who die suddenly have Coronary artery disease (CAD). The causes of DCM can be classified as acquired, sporadic, familial and associated with other syndromic disorders (syndromic DCM) such as Barth syndrome and Alstrom syndrome. 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 syndromic DCM and responsible for the SCD. This study describes the clinical and molecular finding in one consanguineous Saudi family diagnosed as syndromic dilated cardiomyopathy. Whole exome sequencing was performed on genomic DNA extracted from whole blood of the proband and his affected brother. The results revealed a novel homozygous pathogenic mutation (c.2938 dupA) in exon 8 of ALMS1 gene that results in a stop premature truncating mutation at the codon 980 of the protein in both the proband and his brother, which causing Alstrom syndrome (ALMS; OMIM 203800). The mutation was confirmed by Sanger sequencing. This study points out Alstrom syndrome as the known cause for dilated cardiomyopathy in children and mis-diagnosis are common owing to its rarity and age-dependent emergence of multisystem clinical manifestations. Also, we highlight the phenotypic expression variability, existing in the affected members with the same mutation, aiming to enhance earlier diagnosis, treating and managing the ALMS patients. This study emphasizes the utility of exome sequencing in clinical practice. Finally, identification of the exact disease-causing mutation in the proband helps in clearly determining the pattern of inheritance and thereby in appropriate counselling of the family about the recurrence risk in future offspring. 
Supervisor : Prof.Dr. Jumana Al-Aama Prof.Dr. Noor Ahmad Shaik 
Thesis Type : Master Thesis 
Publishing Year : 1441 AH
2020 AD 
Co-Supervisor : Prof.Dr. Noor Ahmad Shaik 
Added Date : Sunday, June 7, 2020 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
فاتن عبد الله القحطانيAL Qahtani, Faten AbdullahResearcherMaster 

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