title: Atrial fibrillation and NPPA gene p.S64R mutation: are cardiologists helpless spectators of healthy mutation carriers?
abstract: OBJECTIVE
  Heterozygous p.(Ser64Arg) mutation in the natriuretic peptide precursor A gene has been associated with atrial fibrillation in the presence of common single nucleotide polymorphisms (rs10033464 and rs2200733; 4q25) that would act as modifiers.
  
  
  METHODS
  We screened natriuretic peptide precursor A gene in 583 individuals and identified three unrelated carriers of the p.(Ser64Arg) mutation (0.5%).
  
  
  RESULTS
  Only one of the three mutation carriers had episodes of atrial fibrillation. Cascade screening of the three families identified seven additional mutation carriers, none showing atrial fibrillation. The patients with atrial fibrillation also carried the rs2200733, which was however found in four additional nonatrial fibrillation family members and carriers of the p.(Ser64Arg). The prevalence of atrial fibrillation in p.(Ser64Arg) carriers was 10% and in those combining the mutation with the risk single nucleotide polymorphisms was 20%. In the unique mutated patient with atrial fibrillation, the arrhythmias was refractory to both pharmacological and ablation treatment, during 16 years of follow-up; his electrophysiological phenotype was characterized by short atrial cycle lengths with a median value of 131 ms that suggests shortening of atrial action potential.
  
  
  CONCLUSIONS
  The prevalence of p.(Ser64Arg) mutation is low in the general population as is the prevalence of atrial fibrillation in mutation carriers (1/10). Atrial fibrillation in the affected mutated patient was lone at onset and progressively evolved with peculiar electrophysiological patterns.
authors.affiliation: aDepartment of Cardiology, Santa Chiara HospitalbHealthcare Research and Innovation Program. PAT-FBKcDepartment of Physics, University of Trento, Povo, TrentodCentre for Inherited Cardiovascular Diseases, IRCCS Foundation, Policlinico San Matteo, Pavia, ItalyeMayo Clinic, 200 1st St Sw, Rochester, MN 55905-0001, USA.
authors.forename: Marcello
authors.initials: M
authors.lastname: Disertori
authors.forename: Michela
authors.initials: M
authors.lastname: Masè
authors.forename: Nupoor
authors.initials: N
authors.lastname: Narula
authors.forename: Silvia
authors.initials: S
authors.lastname: Mazzola
authors.forename: Elena C
authors.initials: EC
authors.lastname: dal Piaz
authors.forename: Silvia
authors.initials: S
authors.lastname: Quintarelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cristoforetti
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Marini
authors.forename: Flavia
authors.initials: F
authors.lastname: Ravelli
authors.forename: Eloisa
authors.initials: E
authors.lastname: Arbustini
mesh_terms: D001281:Atrial Fibrillation / Q000453:epidemiology / Q000235:genetics*; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D003430:Cross-Sectional Studies; D006801:Humans; D007558:Italy / Q000453:epidemiology; D015995:Prevalence
chemical_list: C472955:NPPA protein, human; D009320:Atrial Natriuretic Factor