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Biography |
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Ph.D. Manchester, UK (2002). Director of Clinical Genomics Center (2006-Present)and Assistant Professor of Medical Genetics, Faculty of Medicine, Alexandria University. Senior Researcher in BA HCM National Study.
Fogarty Scholarship Training in Health and Research Ethics, Univeristy of Maryland, USA (2005). Member of the Editorial Board of The Middle East Journal of Medical Genetics.Member of Alexandria Faculty of Medicine Ethics Committee and Alexandria University Research Committee. Served as a scientific reviewer on several national and international organisations for research grants and publication.
Research interest: molecular and clinical genetics of inherited disorders and molecular profiling of cancer.
Education:involved in medical genetics education programs.
Clinical Service:clinical genetics and genetic counseling.
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Abstract |
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Heba Sh. Kassem1,6, Maha Saber-Ayad2,6, Gehan Magdy3, Iacopo Olivotto4, Franco Cecchi4, Magdi Yacoub5 and the BA HCM Consortium6
1. Pathology Department and Clinical Genomics Centre, Alexandria Faculty of Medicine, Egypt 2. Pharmacology Department, Cairo Faculty of Medicine, Egypt. 3.Cardiology Department, Alexandria Faculty of Medicine. 4. Cardiology Department, University of Careggi, Florence, Italy. 5. Imperial College, London, UK. 6. BA- HCM Consortium involves the Egyptian Cardiology Consultants referring HCM patients to the BA-HCM Research Center under the auspice of Bibliotheca Alexandrina, Alexandria, Egypt.
Introduction:
Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease at both clinical and molecular levels. Although the incidence of HCM appears constant in different parts of the world (1 in 500), its phenotypic and genetic features could vary in different populations. A national study is being conducted under the auspice of the Bibliotheca Alexandrina.
Methods and Results:
From 2007-2009, 130 unrelated index HCM patients from across Egypt were recruited from the National HCM Clinics. Thirty two HCM cases are familial (24.6%). Mean age of the patients is 35 ± 18 years (1.5 - 70 years; 91 males). Genetic testing was undertaken for 100 patients (the first cohort) applying genomic analysis for all coding sequence and splice sites of 3 commonly involved sarcomeric genes: cardiac myosin binding protein C (cMyBPC), β myosin heavy chain (MyH7) and cardiac troponin T (TNNT2). Initial screening for mutation was determined through heteroduplex analysis using DHPLC (WAVETM Transgenonmics), followed by automated sequencing of any detected variants or unique profiles in the patient series and variants were tested in 100 healthy controls.
The highest frequency of mutations were detected in cMyBPC3 (n=31/T). Mutations were detected in 29 index patients in MyBPC3. These were 12 missense, 6 frameshift, 4 non sense, 2 splice site mutations and 7 intronic single nucleotide mutations of uncertain significance. Two patients were compound heterozygotes. Genetic analysis of MyH7 and TNNT2 are ongoing and so far detected 12 missense mutations, a single non sense mutation and a single frame shift mutation in the former and 2 missense mutations and a variant of point mutation in intronic sequence of undetermined clinical significance in the latter. While some of the pathogenic mutations detected in βMyH7 were previously reported in other populations, only one of the detected mutations in cMyBPC3, and none of the TNNT2 mutations were previously reported. Two of the patients are double heterozygote one for mutations in both MyBPC3 and TNNT2 genes and another in MyBPC3 and MyH7. Study of genotype and phenotype correlations is currently under investigation through close collaboration between the genetics and cardiology members of the national study team.
Conclusion:
This study is the first to provide genetic data of HCM among Egyptians, which could help the global understanding of HCM and enhance the management of the disease in Egypt.
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