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Abstract

Title: Preliminary Results and Clinical Relevance of Next Generation Sequencing in Hypertrophic Cardiomyopathy Patients in Qatar. Kholoud Al-Shafai 1, Despina Sanoudou 1,2, Paul Barton 3 , Lama Shuayb 1 , Emmeleia Nana 2 , Pothitos Pitychoutis 2 , Rachel Buchan 3 , Roddy Walsh 3 , Stuart Cook 3, Magdi Yacoub 1,3, Mohammed Alhashemi 4 1 Qatar Cardiovascular Research Center (QCRC), Qatar Foundation, Doha, Qatar, 2 Department of Pharmacology, Medical School, University of Athens ,Greece, 3National Heart & Lung Institute, Imperial College London, London, UK. 4Cardiac OPD and Rehabilitation, Heart Hospital, Doha, Qatar. Hypertrophic cardiomyopathy (HCM) is the most common inherited heart muscle disease with a prevalence of 1 in 500 in the general population. HCM exhibits a remarkable clinical and genetic heterogeneity, with over 30 genes being implicated so far. However, the full spectrum of genes and mutations leading to HCM remains to be discovered to help the understanding of genotype-phenotype relationship and its clinical implications. Next generation sequencing (NGS) technologies are powerful tools to study these issues. Here, we utilized NGS technologies to sequence the exomes of over 170 genes including all known HCM genes. Preliminary results of seventeen HCM patients recruited at the Heart Hospital-Qatar is presented, with particular reference to the clinical implications of NGS in early disease detection, diagnosis and disease management. Different previously known HCM disease-causing genetic variants were detected, within sarcomeric genes including TNNI3, MYBPC3, MYL3 and MYH7. Patients carrying those variants were offered genetic counseling and advised for clinical and genetic screening of relatives, leading to the early detection of HCM in a 13 years old boy, coupled with efforts to detect genotype-positive phenotype-negative relatives. Of particular interest are genetic variants found within PRKAG2, NEXN that have not been previously described in HCM and need to be further assessed and screened in relatives. In addition, two genetic variants were detected in SOS1 and RAF1 that were previously related to Noonan Syndrome leading to the diagnosis of Noonan syndrome variants in these patients with cardiac hypertrophy associated phenotype. This is an ongoing program which is expected to yield further valuable information which could influence the management in these patients.

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/content/papers/10.5339/qfarf.2013.BIOP-048
2013-11-20
2019-11-22
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