title: A low prevalence of MYH7/MYBPC3 mutations among familial hypertrophic cardiomyopathy patients in India.
abstract: Familial Hypertrophic Cardiomyopathy (FHC) is an autosomal dominant disorder affecting the cardiac muscle and exhibits varied clinical symptoms because of genetic heterogeneity. Several disease causing genes have been identified and most code for sarcomere proteins. In the current study, we have carried out clinical and molecular analysis of FHC patients from India. FHC was detected using echocardiography and by analysis of clinical symptoms and family history. Disease causing mutations in the β-cardiac myosin heavy chain (MYH7) and Myosin binding protein C3 (MYBPC3) genes were identified using Polymerase Chain Reaction-Deoxyribose Nucleic Acid (PCR-DNA) sequencing. Of the 55 patient samples screened, mutations were detected in only nineteen in the two genes; MYBPC3 mutations were identified in 12 patients while MYH7 mutations were identified in five, two patients exhibited double heterozygosity. All four MYH7 mutations were missense mutations, whereas only 3/9 MYPBC3 mutations were missense mutations. Four novel mutations in MYBPC3 viz. c.456delC, c.2128G>A (p.E710K), c.3641G>A (p.W1214X), and c.3656T>C (p.L1219P) and one in MYH7 viz. c.965C>T (p.S322F) were identified. A majority of missense mutations affected conserved amino acid residues and were predicted to alter the structure of the corresponding mutant proteins. The study has revealed a greater frequency of occurrence of MYBPC3 mutations when compared to MYH7 mutations.
authors.affiliation: Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Nampally, Hyderabad, India. bashyam@cdfd.org.in
authors.forename: Murali D
authors.initials: MD
authors.lastname: Bashyam
authors.forename: Guroji
authors.initials: G
authors.lastname: Purushotham
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Chaudhary
authors.forename: Katika Madhumohan
authors.initials: KM
authors.lastname: Rao
authors.forename: Vishal
authors.initials: V
authors.lastname: Acharya
authors.forename: Tabrez A
authors.initials: TA
authors.lastname: Mohammad
authors.forename: Hampapathalu A
authors.initials: HA
authors.lastname: Nagarajaram
authors.forename: Vuppaladadhiam
authors.initials: V
authors.lastname: Hariram
authors.forename: Calambur
authors.initials: C
authors.lastname: Narasimhan
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D024722:Cardiac Myosins / Q000737:chemistry / Q000235:genetics*; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D017124:Conserved Sequence; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D020125:Mutation, Missense; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA; D055815:Young Adult; D000099163:Myosin Binding Protein C
chemical_list: D024722:Cardiac Myosins; D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D007703:Peptidyl-Dipeptidase A; D000099163:Myosin Binding Protein C; C501641:MYH7 protein, human