Autosomal recessive atrial dilated cardiomyopathy with standstill evolution associated with mutation of Natriuretic Peptide Precursor A

Marcello Disertori, Silvia Quintarelli, Maurizia Grasso, Andrea Pilotto, Nupoor Narula, Valentina Favalli, Camilla Canclini, Marta Diegoli, Silvia Mazzola, Massimiliano Marini, Maurizio Del Greco, Roberto Bonmassari, Michela Masè, Flavia Ravelli, Claudia Specchia, Eloisa Arbustini

Research output: Contribution to journalArticle

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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. Methods and 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.

Original languageEnglish
Pages (from-to)27-36
Number of pages10
JournalCirculation: Cardiovascular Genetics
Volume6
Issue number1
DOIs
Publication statusPublished - Feb 2013

Fingerprint

Natriuretic Peptides
Dilated Cardiomyopathy
Mutation
Dilatation
Atrial Natriuretic Factor
Left Ventricular Function
Phenotype
Inborn Genetic Diseases
Missense Mutation
Rare Diseases
Italy
Genes
Cardiac Arrhythmias
Serum

Keywords

  • Atrial cardiomyopathy
  • Atrial natriuretic factor
  • Atrial standstill
  • Genetics
  • Natriuretic Peptide Precursor A gene

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)
  • Genetics

Cite this

Autosomal recessive atrial dilated cardiomyopathy with standstill evolution associated with mutation of Natriuretic Peptide Precursor A. / Disertori, Marcello; Quintarelli, Silvia; Grasso, Maurizia; Pilotto, Andrea; Narula, Nupoor; Favalli, Valentina; Canclini, Camilla; Diegoli, Marta; Mazzola, Silvia; Marini, Massimiliano; Del Greco, Maurizio; Bonmassari, Roberto; Masè, Michela; Ravelli, Flavia; Specchia, Claudia; Arbustini, Eloisa.

In: Circulation: Cardiovascular Genetics, Vol. 6, No. 1, 02.2013, p. 27-36.

Research output: Contribution to journalArticle

Disertori, M, Quintarelli, S, Grasso, M, Pilotto, A, Narula, N, Favalli, V, Canclini, C, Diegoli, M, Mazzola, S, Marini, M, Del Greco, M, Bonmassari, R, Masè, M, Ravelli, F, Specchia, C & Arbustini, E 2013, 'Autosomal recessive atrial dilated cardiomyopathy with standstill evolution associated with mutation of Natriuretic Peptide Precursor A', Circulation: Cardiovascular Genetics, vol. 6, no. 1, pp. 27-36. https://doi.org/10.1161/CIRCGENETICS.112.963520
Disertori, Marcello ; Quintarelli, Silvia ; Grasso, Maurizia ; Pilotto, Andrea ; Narula, Nupoor ; Favalli, Valentina ; Canclini, Camilla ; Diegoli, Marta ; Mazzola, Silvia ; Marini, Massimiliano ; Del Greco, Maurizio ; Bonmassari, Roberto ; Masè, Michela ; Ravelli, Flavia ; Specchia, Claudia ; Arbustini, Eloisa. / Autosomal recessive atrial dilated cardiomyopathy with standstill evolution associated with mutation of Natriuretic Peptide Precursor A. In: Circulation: Cardiovascular Genetics. 2013 ; Vol. 6, No. 1. pp. 27-36.
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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. Methods and 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.",
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T1 - Autosomal recessive atrial dilated cardiomyopathy with standstill evolution associated with mutation of Natriuretic Peptide Precursor A

AU - Disertori, Marcello

AU - Quintarelli, Silvia

AU - Grasso, Maurizia

AU - Pilotto, Andrea

AU - Narula, Nupoor

AU - Favalli, Valentina

AU - Canclini, Camilla

AU - Diegoli, Marta

AU - Mazzola, Silvia

AU - Marini, Massimiliano

AU - Del Greco, Maurizio

AU - Bonmassari, Roberto

AU - Masè, Michela

AU - Ravelli, Flavia

AU - Specchia, Claudia

AU - Arbustini, Eloisa

PY - 2013/2

Y1 - 2013/2

N2 - 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. Methods and 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.

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