title: Mutational screening of phospholamban gene in hypertrophic and idiopathic dilated cardiomyopathy and functional study of the PLN -42 C>G mutation.
abstract: BACKGROUND
  Phospholamban is an endogenous sarcoplasmic reticulum calcium ATPase inhibitor with a regulatory effect on cardiac contraction/relaxation coupling. Mutations in the phospholamban gene (PLN) have been associated with primary cardiomyopathies.
  
  
  OBJECTIVE
  To screen for PLN mutations in our population of patients with primary cardiomyopathies and to perform functional analysis of the mutations identified.
  
  
  METHODS
  We performed SSCP mutational screening and DNA sequencing of the PLN gene in 186 patients with either hypertrophic or dilated cardiomyopathy. To study promoter strength we constructed reporter plasmids containing the luciferase gene and performed transient transfection analysis in C6 and C2C12 cell lines.
  
  
  RESULTS
  The PLN -42 C>G mutation was found in one patient with late onset familial apical hypertrophic cardiomyopathy. This mutation decreased phospholamban promoter activity by 43% and 47%, in C6 and C2C12 cell lines respectively. One son had mild apical hypertrophic cardiomyopathy and carried the mutation, another son with normal ECG and echocardiogram also had the mutation.
  
  
  CONCLUSIONS
  The PLN -42 C>G mutation is associated with a benign form of apical hypertrophic cardiomyopathy in this family, though the presence of a healthy adult carrier suggests that other genetic and environmental factors could be involved. Otherwise, mutations in the PLN gene are not a frequent cause of cardiomyopathies in our population.
authors.affiliation: Hospital Universitario Juan Canalejo, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Medin
authors.forename: Manuel
authors.initials: M
authors.lastname: Hermida-Prieto
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Monserrat
authors.forename: Rafael
authors.initials: R
authors.lastname: Laredo
authors.forename: Jose Carlos
authors.initials: JC
authors.lastname: Rodriguez-Rey
authors.forename: Xustox
authors.initials: X
authors.lastname: Fernandez
authors.forename: Alfonso
authors.initials: A
authors.lastname: Castro-Beiras
mesh_terms: D002135:Calcium-Binding Proteins / Q000235:genetics*; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging / Q000235:genetics*; D002460:Cell Line; D003596:Cytosine; D004252:DNA Mutational Analysis; D004562:Electrocardiography; D006147:Guanine; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D014162:Transfection; D014463:Ultrasonography; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D003596:Cytosine; D006147:Guanine; D000099211:Phospholamban