Sarcomeric proteins and Familial Hypertrophic Cardiomyopathy: Linking mutations in structural proteins to complex cardiovascular phenotypes

Research output: Contribution to journalReview articlepeer-review

138 Scopus citations


Hypertrophic Cardiomyopathy (HCM) is a relatively common primary cardiac disorder defined as the presence of a hypertrophied left ventricle in the absence of any other diagnosed etiology. HCM is the most common cause of sudden cardiac death in young people which often occurs without precedent symptoms. The overall clinical phenotype of patients with HCM is broad, ranging from a complete lack of cardiovascular symptoms to exertional dyspnea, chest pain, and sudden death, often due to arrhythmias. To date, 270 independent mutations in nine sarcomeric protein genes have been linked to Familial Hypertrophic Cardiomyopathy (FHC), thus the clinical variability is matched by significant genetic heterogeneity. While the final clinical phenotype in patients with FHC is a result of multiple factors including modifier genes, environmental influences and genotype, initial screening studies had suggested that individual gene mutations could be linked to specific prognoses. Given that the sarcomeric genes linked to FHC encode proteins with known functions, a vast array of biochemical, biophysical and physiologic experimental approaches have been applied to elucidate the molecular mechanisms that underlie the pathogenesis of this complex cardiovascular disorder. In this review, to illustrate the basic relationship between protein dysfunction and disease pathogenesis we focus on representative gene mutations from each of the major structural components of the cardiac sarcomere: the thick filament (βMyHC), the thin filament (cTnT and Tm) and associated proteins (MyBP-C). The results of these studies will lead to a better understanding of FHC and eventually identify targets for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)237-248
Number of pages12
JournalHeart Failure Reviews
Issue number3
StatePublished - Sep 1 2005
Externally publishedYes


  • Hypertrophic cardiomyopathy
  • Sarcomeric proteins
  • Transgenic models

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Sarcomeric proteins and Familial Hypertrophic Cardiomyopathy: Linking mutations in structural proteins to complex cardiovascular phenotypes'. Together they form a unique fingerprint.

Cite this