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

DOI: 10.1186/1471-2350-13-17

Keywords: Hypertrophic cardiomyopathy, Gene-based diagnosis, High Resolution Melting, Sarcomere proteins, CSRP3 gene

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Abstract:

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 (HCM) is the most common monogenic disease of the cardiovascular trait affecting 1:500 individuals in the general population [1-3]. HCM is classically characterized by unexplained left ventricular hypertrophy (LVH) and distinct histopathological features comprising myocyte disarray and interstitial fibrosis [1-3]. Clinical evaluation may be triggered in response to symptoms, in asymptomatic individuals in the course of a family screening, or after detection of a systolic murmur or an abnormal electrocardiogram (ECG). HCM diagnosis is typically performed by the identification of unexplained LVH on cardiac imaging studies. Nevertheless, the morphologic pattern of LVH is not closely predictive of the severity of symptoms or prognosis [1]. HCM is a complex and heterogeneous disease with remarkable diversity in th

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