Abstract

Background: Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden cardiac death (SCD) in children and young adults and is the most frequent genetically determined cardiovascular disease following autosomal dominant pattern of inheritance. A number of genes have been shown to be responsible for HCM including MYBPC3. Cmybc, the protein encoded by MYBPC3 is a sarcomeric thick filament protein that interacts with titin, myosin, and actin to control sarcomeric gathering. Mutations in the MYBPC3 gene have been found to be associated with a history of sudden cardiac death in HCM patients. The main objective of the present study was to investigate the type and frequency of mutations in the MYBPC3 gene in HCM patients from the North-West of Iran.
Methods: All the exons and exon-intron flanking regions of the MYBPC3 gene were assessed by PCR-SSCP, and the PCR products with divergent pattern of bands on polyacrylamide gel were sent for bi-directional sequencing.
Results: Mutational screening of a cohort of 42 HCM cases led to the identification of 14 MYBPC3 variations. Three cases out of those variations were frameshift, 1 case was splice site, 3 cases were missense, 2 cases were synonymous, and 5 cases were intronic variants. MYBPC3 mutations (28.5%) represent the most prevalent cause of inherited HCM. The age of onset was 39.3 in MYBPC3 carrier patients. Multiple gene mutations were recognized in 1 case (2.3%).
Conclusions: The results obtained from the present study indicate a significant role of MYBPC3 gene mutations in HCM disease and can be used for pre-symptomatic diagnosis of at risk family members of affected individuals.

DOI: 10.7754/Clin.Lab.2014.141134