title: MYBPC3 gene variations in hypertrophic cardiomyopathy patients in India.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM) is a complex cardiac muscular disorder, inherited as an autosomal dominant disease with variable penetrance. Cardiac myosin-binding protein C (MyBPC) is the predominant myosin-binding protein isoform in the heart muscle. One hundred forty-seven mutations have been detected in MYBPC3, accounting for 15% of all HCM cases.
  
  
  OBJECTIVE
  To screen exons 16, 18, 19, 22, 24, 28, 30, 31 and 34 in the MYBPC3 gene in Indian HCM patients.
  
  
  METHODS
  Sixty control and 95 HCM samples were collected from cardiology units of the CARE Hospital (Nampally, Banjara Hills, Secunderabad, India) for genomic DNA isolation followed by polymerase chain reaction and single-stranded conformational polymorphism analysis.
  
  
  RESULTS
  Screening of the exons revealed two variations - one novel frame shift mutation in exon 19 at the nucleotide position 11577-11578 and one novel single nucleotide polymorphism (SNP) in codon 1093 of exon 31, coding for glycine with a C>T transition (GGC/GGT), in addition to the seven known SNPs mainly in the intronic region and one known missense mutation D770N in this population.
  
  
  CONCLUSIONS
  The novel frame shift mutation identified in exon 19, D570fs, with the insertion of an adenine residue in codon 570 coding for aspartate, results in a premature termination codon that produces a truncated protein lacking myosin- and titin-binding sites, explaining the role of the nonsense-mediated decay pathway. A novel SNP identified in codon 1093 of exon 31 was found to be a synonymous codon, which may have a regulatory effect at the translational level, attributing to affinity differences between codon-anticodon interactions. The screening of this gene may be relevant in the Indian context.
authors.affiliation: Department of Genetics, Osmania University, Jamai Osmania PO, Hyderabad, Andhra Pradesh, India.
authors.forename: Reena R
authors.initials: RR
authors.lastname: Tanjore
authors.forename: Advithi
authors.initials: A
authors.lastname: Rangaraju
authors.forename: P G
authors.initials: PG
authors.lastname: Kerkar
authors.forename: Narsimhan
authors.initials: N
authors.lastname: Calambur
authors.forename: Pratibha
authors.initials: P
authors.lastname: Nallari
mesh_terms: D000328:Adult; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D018389:Codon, Nonsense; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D005820:Genetic Testing; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D018389:Codon, Nonsense; D000099163:Myosin Binding Protein C