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Atrial fibrillation and NPPA gene p.S64R mutation: are cardiologists helpless spectators of healthy mutation carriers?

Disertori, Marcello; Masè, Michela; Narula, Nupoor; Mazzola, Silvia; Piaz, Elena C. dal; Quintarelli, Silvia; Cristoforetti, Alessandro; Marini, Massimiliano; Ravelli, Flavia; Arbustini, Eloisa

Journal of Cardiovascular Medicine: March 2016 - Volume 17 - Issue 3 - p 177–180
doi: 10.2459/JCM.0000000000000302
Original articles

Aims: 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.

Conclusion: 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.

aDepartment of Cardiology, Santa Chiara Hospital

bHealthcare Research and Innovation Program. PAT-FBK

cDepartment of Physics, University of Trento, Povo, Trento

dCentre for Inherited Cardiovascular Diseases, IRCCS Foundation, Policlinico San Matteo, Pavia, Italy

eMayo Clinic, 200 1st St Sw, Rochester, MN 55905-0001, USA

Correspondence to Professor Eloisa Arbustini, Centre for Inherited Cardiovascular Diseases, IRCCS Foundation, Policlinico San Matteo, Piazzale Golgi 19, 27100 Pavia, Italy Tel: +39 0382 501206; fax: +39 0382 501893; e-mail: e.arbustini@smatteo.pv.it

Received 9 February, 2015

Revised 17 May, 2015

Accepted 11 June, 2015

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© 2016 Italian Federation of Cardiology. All rights reserved.