Molecular analysis of sarcomeric and non-sarcomeric genes in patients with hypertrophic cardiomyopathy

Irene Bottillo, Daniela D'Angelantonio, Viviana Caputo, Alessandro Paiardini, Martina Lipari, Carmelilia De Bernardo, Diana Giannarelli, Antonio Pizzuti, Silvia Majore, Marco Castori, Elisabetta Zachara, Federica Re, Paola Grammatico

Research output: Contribution to journalArticlepeer-review


Background: Hypertrophic cardiomyopathy (HCM) is a common genetic heart disorder characterized by unexplained left ventricle hypertrophy associated with non-dilated ventricular chambers. Several genes encoding heart sarcomeric proteins have been associated to HCM, but a small proportion of HCM patients harbor alterations in other non-sarcomeric loci. The variable expression of HCM seems influenced by genetic modifier factors and new sequencing technologies are redefining the understanding of genotype-phenotype relationships, even if the interpretations of the numerous identified variants pose several challenges. Methods and results: We investigated 62 sarcomeric and non-sarcomeric genes in 41 HCM cases and in 3 HCM-related disorders patients. We employed an integrated approach that combines multiple tools for the prediction, annotation and visualization of functional variants. Genotype-phenotype correlations were carried out for inspecting the involvement of each gene in age onset and clinical variability of HCM. The 80% of the non-syndromic patients showed at least one rare non-synonymous variant (nsSNV) and among them, 58% carried alterations in sarcomeric loci, 14% in desmosomal and 7% in other non-sarcomeric ones without any sarcomere change. Statistical analyses revealed an inverse correlation between the number of nsSNVs and age at onset, and a relationship between the clinical variability and number and type of variants. Conclusions: Our results extend the mutational spectrum of HCM and contribute in defining the molecular pathogenesis and inheritance pattern(s) of this condition. Besides, we delineate a specific procedure for the identification of the most likely pathogenetic variants for a next generation sequencing approach embodied in a clinical context.

Original languageEnglish
Pages (from-to)227-235
Number of pages9
Issue number2
Publication statusPublished - Feb 15 2016


  • Genetic testing
  • HCM
  • Hypertrophic cardiomyopathy
  • Next generations sequencing
  • NGS
  • Sarcomere

ASJC Scopus subject areas

  • Genetics


Dive into the research topics of 'Molecular analysis of sarcomeric and non-sarcomeric genes in patients with hypertrophic cardiomyopathy'. Together they form a unique fingerprint.

Cite this