Open Access Highly Accessed Research article

High resolution melting: improvements in the genetic diagnosis of hypertrophic cardiomyopathy in a Portuguese cohort

Susana Santos123, Vanda Marques23, Marina Pires2, Leonor Silveira2, Helena Oliveira2, Vasco Lança5, Dulce Brito6, Hugo Madeira6, J Fonseca Esteves7, António Freitas7, Isabel M Carreira48, Isabel M Gaspar109, Carolino Monteiro34 and Alexandra R Fernandes1112*

Author Affiliations

1 Centro de Química Estrutural, Instituto Superior Técnico, Technical University of Lisbon, Lisbon, Portugal

2 Faculdade de Engenharia e Ciências Naturais, Universidade Lusófona de Humanidades e Tecnologias, Lisbon, Portugal

3 Faculdade de Farmácia, University of Lisbon, Lisbon, Portugal

4 CENCIFOR - Forensic Sciences Centre, Coimbra, Portugal

5 Centro de Metabolismo e Endocrinologia, Faculty of Medicine, University of Lisbon, Lisbon, Portugal

6 Centro de Cardiologia, Faculty of Medicine, University of Lisbon, Lisbon, Portugal

7 Centro de Medicina Desportiva de Lisboa, Lisboa, Portugal

8 Laboratory of Cytogenetics and Genomics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

9 Genética Médica, Hospital Egas Moniz, Baltimore, MD, USA

10 Cardiogenética, Hospital Santa Cruz, Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal

11 Departamento Ciências da Vida, Faculty of Scienses and Technologies, Universidade Nova de Lisboa, Lisboa, Portugal

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BMC Medical Genetics 2012, 13:17  doi:10.1186/1471-2350-13-17

Published: 19 March 2012



Hypertrophic Cardiomyopathy (HCM) is a complex myocardial disorder with a recognized genetic heterogeneity. The elevated number of genes and mutations involved in HCM limits a gene-based diagnosis that should be considered of most importance for basic research and clinical medicine.


In this report, we evaluated High Resolution Melting (HRM) robustness, regarding HCM genetic testing, by means of analyzing 28 HCM-associated genes, including the most frequent 4 HCM-associated sarcomere genes, as well as 24 genes with lower reported HCM-phenotype association. We analyzed 80 Portuguese individuals with clinical phenotype of HCM allowing simultaneously a better characterization of this disease in the Portuguese population.


HRM technology allowed us to identify 60 mutated alleles in 72 HCM patients: 49 missense mutations, 3 nonsense mutations, one 1-bp deletion, one 5-bp deletion, one in frame 3-bp deletion, one insertion/deletion, 3 splice mutations, one 5'UTR mutation in MYH7, MYBPC3, TNNT2, TNNI3, CSRP3, MYH6 and MYL2 genes. Significantly 22 are novel gene mutations.


HRM was proven to be a technique with high sensitivity and a low false positive ratio allowing a rapid, innovative and low cost genotyping of HCM. In a short return, HRM as a gene scanning technique could be a cost-effective gene-based diagnosis for an accurate HCM genetic diagnosis and hopefully providing new insights into genotype/phenotype correlations.

Hypertrophic cardiomyopathy; Gene-based diagnosis; High Resolution Melting; Sarcomere proteins; CSRP3 gene