Early Results of Sarcomeric Gene Screening from the Egyptian National BA-HCM Program

• Published in: Journal of cardiovascular translational research 2013-02, Vol.6 (1), p.65-80
• Main Authors: Kassem, Heba Sh, Azer, Remon S., Ayad, Maha S., Moharem-Elgamal, Sarah, Magdy, Gehan, Elguindy, Ahmed, Cecchi, Franco, Olivotto, Iacopo, Yacoub, Magdi H.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Biomedical Engineering and Bioengineering; Biomedicine; Cardiac Myosins - genetics; Cardiology; Cardiomyopathy, Hypertrophic - epidemiology; Cardiomyopathy, Hypertrophic - genetics; Carrier Proteins - genetics; Child; Child, Preschool; CpG Islands; DNA Mutational Analysis; Egypt - epidemiology; Female; Genetic Predisposition to Disease; Genetic Testing - methods; Human Genetics; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; Myosin Heavy Chains - genetics; Phenotype; Prognosis; Sarcomeres; Troponin T - genetics; Young Adult
• ISSN: 1937-5387; 1937-5395
• DOI: 10.1007/s12265-012-9425-0

The present study comprised sarcomeric genotyping of the three most commonly involved sarcomeric genes: MYBPC3 , MYH7 , and TNNT2 in 192 unrelated Egyptian hypertrophic cardiomyopathy (HCM) index patients. Mutations were detected in 40 % of cases. Presence of positive family history was significantly ( p  = 0.002) associated with a higher genetic positive yield (49/78, 62.8 %). The majority of the detected mutations in the three sarcomeric genes were novel (40/62, 65 %) and mostly private (47/62, 77 %). Single nucleotide substitution was the most frequently detected mutation type (51/62, 82 %). Over three quarters of these substitutions (21/27, 78 %) involved CpG dinucleotide sites and resulted from C > T or G > A transition in the three analyzed genes, highlighting the significance of CpG high mutability within the sarcomeric genes examined. This study could aid in global comparative studies in different ethnic populations and constitutes an important step in the evolution of the integrated clinical, translational, and basic science HCM program.