title: Mutation analysis of the natriuretic peptide precursor B (NPPB) gene in patients with hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM) is a genetically heterogenous disease caused by mutations in genes that primarily encode sarcomeric proteins. No mutation is identified in up to 40% of HCM patients, suggesting other causative genes exist. Natriuretic peptide precursor B (NPPB; also known as "BNP") is a cardiac hormone involved in body fluid homeostasis and cardiac myocyte growth. NPPB concentrations are markedly increased in patients with ventricular hypertrophy, and it is therefore possible mutations in the NPPB gene could cause HCM.
  
  
  METHODS
  Genomic DNA was extracted from peripheral blood in 238 consecutive probands with HCM. The coding regions and intron/exon boundaries in the NPPB gene were amplified by PCR, and products were screened for sequence variants using high-performance liquid chromatography, followed by direct DNA sequencing.
  
  
  RESULTS
  Four sequence variants in the NPPB gene were identified in 9 of the 238 probands screened. Two of the variants were intronic, one was a synonymous variant at codon 79, and the final variant resulted in an amino acid substitution from arginine to histidine at codon 47 (Arg47His). The Arg47His variant was identified in a control population consisting of 204 chromosomes at an allelic frequency of 0.5%, and is therefore unlikely to cause disease.
  
  
  CONCLUSIONS
  No disease causing mutations were identified in the NPPB gene in this cohort, indicating that mutations in this gene are unlikely to be responsible for HCM.
authors.affiliation: Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, Australia.
authors.forename: Christine
authors.initials: C
authors.lastname: Chiu
authors.forename: Jodie
authors.initials: J
authors.lastname: Ingles
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Lind
authors.forename: Christopher
authors.initials: C
authors.lastname: Semsarian
mesh_terms: D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D020097:Natriuretic Peptide, Brain / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*
chemical_list: D011498:Protein Precursors; D020097:Natriuretic Peptide, Brain