title: Autosomal recessive atrial dilated cardiomyopathy with standstill evolution associated with mutation of Natriuretic Peptide Precursor A.
abstract: BACKGROUND
  Atrial dilatation and atrial standstill are etiologically heterogeneous phenotypes with poorly defined nosology. In 1983, we described 8-years follow-up of atrial dilatation with standstill evolution in 8 patients from 3 families. We later identified 5 additional patients with identical phenotypes: 1 member of the largest original family and 4 unrelated to the 3 original families. All families are from the same geographic area in Northeast Italy.
  
  
  RESULTS
  We followed up the 13 patients for up to 37 years, extended the clinical investigation and monitoring to living relatives, and investigated the genetic basis of the disease. The disease was characterized by: (1) clinical onset in adulthood; (2) biatrial dilatation up to giant size; (3) early supraventricular arrhythmias with progressive loss of atrial electric activity to atrial standstill; (4) thromboembolic complications; and (5) stable, normal left ventricular function and New York Heart Association functional class during the long-term course of the disease. By linkage analysis, we mapped a locus at 1p36.22 containing the Natriuretic Peptide Precursor A gene. By sequencing Natriuretic Peptide Precursor A, we identified a homozygous missense mutation (p.Arg150Gln) in all living affected individuals of the 6 families. All patients showed low serum levels of atrial natriuretic peptide. Heterozygous mutation carriers were healthy and demonstrated normal levels of atrial natriuretic peptide.
  
  
  CONCLUSIONS
  Autosomal recessive atrial dilated cardiomyopathy is a rare disease associated with homozygous mutation of the Natriuretic Peptide Precursor A gene and characterized by extreme atrial dilatation with standstill evolution, thromboembolic risk, preserved left ventricular function, and severely decreased levels of atrial natriuretic peptide.
authors.affiliation: Department of Cardiology, Santa Chiara Hospital, Trento, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Disertori
authors.forename: Silvia
authors.initials: S
authors.lastname: Quintarelli
authors.forename: Maurizia
authors.initials: M
authors.lastname: Grasso
authors.forename: Andrea
authors.initials: A
authors.lastname: Pilotto
authors.forename: Nupoor
authors.initials: N
authors.lastname: Narula
authors.forename: Valentina
authors.initials: V
authors.lastname: Favalli
authors.forename: Camilla
authors.initials: C
authors.lastname: Canclini
authors.forename: Marta
authors.initials: M
authors.lastname: Diegoli
authors.forename: Silvia
authors.initials: S
authors.lastname: Mazzola
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Marini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Del Greco
authors.forename: Roberto
authors.initials: R
authors.lastname: Bonmassari
authors.forename: Michela
authors.initials: M
authors.lastname: Masè
authors.forename: Flavia
authors.initials: F
authors.lastname: Ravelli
authors.forename: Claudia
authors.initials: C
authors.lastname: Specchia
authors.forename: Eloisa
authors.initials: E
authors.lastname: Arbustini
mesh_terms: D000328:Adult; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D001483:Base Sequence; D009202:Cardiomyopathies / Q000235:genetics*; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006325:Heart Atria / Q000002:abnormalities; D006327:Heart Block / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: C472955:NPPA protein, human; D009320:Atrial Natriuretic Factor