Document Details

Document Type : Thesis 
Document Title :
IDENTIFICATION OF NKX2.5 GENE MUTATIONS IN PATIENTS WITH CONGENITAL HEART DEFECTS
في مرضى العيوب الخلقية NKX2.5تحديد طفرات الوراثية في المورث في القلب.
 
Subject : Faculty of Applied Medical Sciences 
Document Language : Arabic 
Abstract : Background: Congenital heart defects (CHDs) are the most common developmental anomaly. The incidence in newborns is approximately 1%. They are the leading cause of mortality among newborns. CHDs result from combined effects of genetic and environmental factors. Genetic factors have a significant role in cardiac development. Any change affects those genes is a primary cause of (CHD). The transcription factors TBX5, GATA4, NKX2.5 are major players. The homeodomain transcription factor NKX2.5 has a major significance among the cardiac genes. It is a transcription factor essential for normal cardiac development and in the determination of myocardial cell fate and the subsequent morphogenesis. This cardiac specific homeobox gene is one of the earliest markers of cardiac mesoderm. NKX2.5 also plays a critical role in the postnatal development of the conduction system. Heart development and adult heart function can be altered by NKX2.5 mutations. The mutation in this gene is causing abnormal protein degradation via Ubiquitin-proteasome system and partial impaired transcription activity Aim of The Study: The aim of this study was to identify mutations in NKX2.5 among patients with different heart defects. Subjects and Methods: The study included 46 congenital heart defects patients and 10 normal control subjects. Patients were referred from King Abdul-Aziz University Hospital (KAUH(, the Pediatric Cardiology Clinic to the Center of Excellence in Genomic Medicine Research(CEGMR). The patients were 23 males and 23 females. Their ages range from 9 days to 14 years. Most of the cases had more than one type of cardiac abnormalities. Two cases, one with Down syndrome and the other one with Edward syndrome were excluded from the study. Polymerase Chain Reaction PCR and DNA sequencing were done to all coding exons of NKX2.5 using automated sequencer. Results: The study identified one mutation in NKX2.5gene in two patients, (Arg25Cys) mutation. Also five previously reported SNPs: rs: 767243751, rs: 2277923, rs: 151314714, rs: 3729753 and rs: 72554028. Conclusion and Recommendations: The association between NKX2.5 mutations and CHD was observed in small percentage of patients in the Western region of Saudi Arabia. More analysis with a larger sample size is needed to understand the entire picture of CHDs and to establish the association between CHDs and the presence of mutations and SNPs. 
Supervisor : Dr. Adeel G Chaudhary 
Thesis Type : Master Thesis 
Publishing Year : 1438 AH
2016 AD 
Added Date : Thursday, January 12, 2017 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
همسه محمد هوساويHawsawi, Hamssa MohammedResearcherMaster 

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