title: Unexpectedly low mutation rates in beta-myosin heavy chain and cardiac myosin binding protein genes in Italian patients with hypertrophic cardiomyopathy.
abstract: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease. Fourteen sarcomeric and sarcomere-related genes have been implicated in HCM etiology, those encoding β-myosin heavy chain (MYH7) and cardiac myosin binding protein C (MYBPC3) reported as the most frequently mutated: in fact, these account for around 50% of all cases related to sarcomeric gene mutations, which are collectively responsible for approximately 70% of all HCM cases. Here, we used denaturing high-performance liquid chromatography followed by bidirectional sequencing to screen the coding regions of MYH7 and MYBPC3 in a cohort (n = 125) of Italian patients presenting with HCM. We found 6 MHY7 mutations in 9/125 patients and 18 MYBPC3 mutations in 19/125 patients. Of the three novel MYH7 mutations found, two were missense, and one was a silent mutation; of the eight novel MYBPC3 mutations, one was a substitution, three were stop codons, and four were missense mutations. Thus, our cohort of Italian HCM patients did not harbor the high frequency of mutations usually found in MYH7 and MYBPC3. This finding, coupled to the clinical diversity of our cohort, emphasizes the complexity of HCM and the need for more inclusive investigative approaches in order to fully understand the pathogenesis of this disease.
authors.affiliation: Instituto di Tecnologie Biomediche, Consiglio Nazionale delle Ricerche, Milan, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Roncarati
authors.forename: Michael V G
authors.initials: MV
authors.lastname: Latronico
authors.forename: Beatrice
authors.initials: B
authors.lastname: Musumeci
authors.forename: Stefania
authors.initials: S
authors.lastname: Aurino
authors.forename: Annalaura
authors.initials: A
authors.lastname: Torella
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Bang
authors.forename: Gloria Saccani
authors.initials: GS
authors.lastname: Jotti
authors.forename: Annibale A
authors.initials: AA
authors.lastname: Puca
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Nigro
authors.forename: Camillo
authors.initials: C
authors.lastname: Autore
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Condorelli
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D024722:Cardiac Myosins / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000453:epidemiology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002637:Chest Pain / Q000453:epidemiology / Q000235:genetics; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012518:Sarcomeres / Q000235:genetics; D000099163:Myosin Binding Protein C
chemical_list: D024722:Cardiac Myosins; D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D000099163:Myosin Binding Protein C; C501641:MYH7 protein, human