title: High resolution melting: improvements in the genetic diagnosis of hypertrophic cardiomyopathy in a Portuguese cohort.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Technical University of Lisbon, Lisbon, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Santos
authors.forename: Vanda
authors.initials: V
authors.lastname: Marques
authors.forename: Marina
authors.initials: M
authors.lastname: Pires
authors.forename: Leonor
authors.initials: L
authors.lastname: Silveira
authors.forename: Helena
authors.initials: H
authors.lastname: Oliveira
authors.forename: Vasco
authors.initials: V
authors.lastname: Lança
authors.forename: Dulce
authors.initials: D
authors.lastname: Brito
authors.forename: Hugo
authors.initials: H
authors.lastname: Madeira
authors.forename: J Fonseca
authors.initials: JF
authors.lastname: Esteves
authors.forename: António
authors.initials: A
authors.lastname: Freitas
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Carreira
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Gaspar
authors.forename: Carolino
authors.initials: C
authors.lastname: Monteiro
authors.forename: Alexandra R
authors.initials: AR
authors.lastname: Fernandes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001699:Biometry; D024722:Cardiac Myosins / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D015331:Cohort Studies; D019295:Computational Biology; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D018995:Myosin Heavy Chains / Q000235:genetics; D009691:Nucleic Acid Denaturation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011174:Portugal; D020107:Troponin T / Q000235:genetics; D055815:Young Adult; D000099163:Myosin Binding Protein C
chemical_list: D024722:Cardiac Myosins; D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D020107:Troponin T; D000099163:Myosin Binding Protein C; C094239:MYH6 protein, human; C501641:MYH7 protein, human; C545568:TNNT2 protein, human