Maximilian G Posch, Laura Thiemann, Pavol Tomasov, Josef Veselka, Nuno Cardim, Monica Garcia-Castro, Eliecer Coto, Andreas Perrot, Christian Geier, Rainer Dietz, Wilhelm Haverkamp, Cemil Ozcelik
Med Sci Monit 2008; 14(7): CR372-374
Familial hypertrophic cardiomyopathy (HCM) is an allelic cardiac disorder characterized by increased ventricular wall mass and sudden cardiac death. A variety of dominant single-gene mutations in sarcomeric genes have been identified, indicating a highly heterogeneous genetic etiology. MYOZ2 encodes for sarcomeric calsarcin-1 located in the myocardial z-disc, a focal point of HCM disease genes. Very recently mutations in MYOZ2 were reported as a cause for HCM. To assess the prevalence of MYOZ2 mutations among European HCM patients, coding exons weree analyzed for genetic variants in 438 patients.
Material and Method: Four hundred thirty-eight patients with HCM in four European cardiovascular centers were recruited. The coding region of MYOZ2 was directly sequenced in all the HCM subjects.
Results: Two non-synonymous polymorphisms in exon 2 (rs17851524) and exon 5 (rs7687613) of MYOZ2 were identified in eight and twenty-two patients, respectively. However, no disease-causing mutations could be identified in this large cohort of HCM patients.
Conclusions: Although a large cohort of more than 400 patients with familial HCM was screened, a disease-associated mutation in MYOZ2 was not identified. When these results are combined with previous reports, it can be concluded that MYOZ2 mutations are rare causes of familial HCM.
Keywords: Polymorphism, Genetic, Humans, Muscle Proteins - genetics, European Continental Ancestry Group - genetics, DNA Mutational Analysis, Carrier Proteins - genetics, Sequence Analysis, DNA, Cardiomyopathy, Hypertrophic, Familial - genetics