Investigations of hot spot regions in MYH7 genes in Iranian hypertrophic cardiomyopathy patients

Background: Hypertrophic cardiomyopathy occurs approximately 1 in 500 people. It is the most common cause of sudden cardiac death in young people. It is the most common cause of sudden cardiac death in young people. The disease is characterized by hypertrophy of left and/or right ventricles and intrventricular septum. Patients could develop serious complications including heart failure, arrhythmias and sudden death. Familial hypertrophic cardiomyopathy is a single gene disorder and has autosomal dominant inheritance. Mutations in at least 11 genes (such as MYH7, MYBPC3 and TNNT2) encoding sarcomeric proteins and possibly in one gene encoding a non-sarcomeric protein (PRKG2) have been associated with hypertrophic cardiomyopathy so far. In this study we focused on exons 13-15 and 19-21 of MYH7 gene and introns located between them, which contain hotspots for so called “malignant mutations” that increase sudden cardiac death risk. Methods: Fifty unrelated Iranian patients with hypertrophic cardiomyopathy were selected sequentially and informed written consent was obtained from them. Genomic DNA was extracted from peripheral venous blood leukocytes by salting-out method. Exons 13-15 and 19-21 of MYH7 gene and their related introns were amplified by polymerase chain reaction. Then PCR products were sequenced. Results: Mutations were detected in fourteen (28%) of the patients. Three mutations were found in exons. We have found a novel mutation, A10419C in exon 14, which was a missense mutation causing N444T substitution. Conclusion: Mutations in the MYH7 gene can be found in patients without a family history of hypertrophic cardiomyopathy. Screening of already known mutations is not helpful and the analysis should be started systematically by testing MYH7 and MYBPC3 and then focus on TNNI3, TNNT2, and MYL. Also, in severe phenotypes, several mutations should be searched.

کلیدواژه ها:

Hypertrophic cardiomyopathy ، MYH7 gene ، beta-myosin heavy chain ، mutation ، Iranian