title: A molecular screening strategy based on beta-myosin heavy chain, cardiac myosin binding protein C and troponin T genes in Italian patients with hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Mutations causing hypertrophic cardiomyopathy (HCM) have been described in nine different genes of the sarcomere. Three genes account for most known mutations: beta-myosin heavy chain (MYH7), cardiac myosin binding protein C (MYBPC3) and cardiac troponin T (TNNT2). Their prevalence in Italian HCM patients is unknown. Thus, we prospectively assessed a molecular screening strategy of these three genes in a consecutive population with HCM from two Italian centres.
  
  
  METHODS
  Comprehensive screening of MYBPC3, MYH7 and TNNT2 was performed in 88 unrelated HCM patients by denaturing high-performance liquid chromatography and automatic sequencing.
  
  
  RESULTS
  We identified 32 mutations in 50 patients (57%); 16 were novel. The prevalence rates for MYBPC3, MYH7 and TNNT2 were 32%, 17% and 2%, respectively. MYBPC3 mutations were 18, including two frameshift, five splice-site and two nonsense. All were 'private' except insC1065 and R502Q, present in three and two patients, respectively. Moreover, E258K was found in 14% of patients, suggesting a founder effect. MYH7 mutations were 12, all missense; seven were novel. In TNNT2, only two mutations were found. In addition, five patients had a complex genotype [i.e. carried a double MYBPC3 mutation (n = 2), or were double heterozygous for mutations in MYBPC3 and MYH7 (n = 3)].
  
  
  CONCLUSIONS
  The first comprehensive evaluation of MYBPC3, MYH7 and TNNT2 in an Italian HCM population allowed a genetic diagnosis in 57% of the patients. These data support a combined analysis of the three major sarcomeric genes as a rational and cost-effective initial approach to the molecular screening of HCM.
authors.affiliation: Genetic Diagnostic Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy. citogenbibl3@ao-careggi.toscana.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Girolami
authors.forename: Iacopo
authors.initials: I
authors.lastname: Olivotto
authors.forename: Ilaria
authors.initials: I
authors.lastname: Passerini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Zachara
authors.forename: Stefano
authors.initials: S
authors.lastname: Nistri
authors.forename: Federica
authors.initials: F
authors.lastname: Re
authors.forename: Silvia
authors.initials: S
authors.lastname: Fantini
authors.forename: Katia
authors.initials: K
authors.lastname: Baldini
authors.forename: Francesca
authors.initials: F
authors.lastname: Torricelli
authors.forename: Franco
authors.initials: F
authors.lastname: Cecchi
mesh_terms: D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016009:Chi-Square Distribution; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D011446:Prospective Studies; D020107:Troponin T / Q000235:genetics*; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D020107:Troponin T; D000099163:Myosin Binding Protein C