Atrial Natriuretic Peptide Frameshift Mutation in Familial Atrial Fibrillation

• Published in: The New England journal of medicine Vol. 359; no. 2; pp. 158 - 165
• Main Authors: Hodgson-Zingman, Denice M, Karst, Margaret L, Zingman, Leonid V, Heublein, Denise M, Darbar, Dawood, Herron, Kathleen J, Ballew, Jeffrey D, de Andrade, Mariza, Burnett, John C, Olson, Timothy M
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 10.07.2008
• Subjects: Action Potentials; Adult; Animals; Atrial Fibrillation - genetics; Atrial Fibrillation - metabolism; Atrial Fibrillation - physiopathology; Atrial Natriuretic Factor - genetics; Atrial Natriuretic Factor - metabolism; Biological and medical sciences; Cardiac dysrhythmias; Cardiology. Vascular system; Chromosome Mapping; Chromosomes, Human, Pair 1; DNA Mutational Analysis; Female; Frameshift Mutation; General aspects; Guanosine Monophosphate - metabolism; Heart; Humans; Male; Medical sciences; Middle Aged; Pedigree; Signal Transduction; White People - genetics; Medicine; Arrhythmia; Family study; Heart disease; Atrial fibrillation; Frameshift mutation; Cardiovascular disease; Atrial natriuretic peptide; Excitability disorder
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa0706300

In a family with hereditary atrial fibrillation, linkage analysis and candidate-gene sequencing identified a frameshift mutation in the atrial natriuretic peptide gene. This mutation segregated with atrial fibrillation in the family and generated a fusion protein that was detected by radioimmunoassay in the plasma of affected family members. The mutant protein caused shortening of the atrial monophasic action potential and the effective refractory period in isolated perfused hearts. In a family with hereditary atrial fibrillation, linkage analysis and candidate-gene sequencing identified a frameshift mutation in the atrial natriuretic peptide gene. Atrial fibrillation is the most common sustained cardiac arrhythmia. Since the lifetime risk of the condition is 25%, it constitutes a growing epidemic in the aging population. 1 , 2 Atrial fibrillation develops as a paroxysmal disorder characterized by rapid, irregular electrical activation of the atria and can be associated with palpitations, syncope, thromboembolic stroke, and congestive heart failure. Valvular, ischemic, hypertensive, and myopathic heart diseases are the most common causes of acquired atrial fibrillation. However, a genetic basis for atrial fibrillation is evident in population-based studies 3 , 4 and in a subgroup of patients with familial disease. 5 , 6 Human genetics investigations have . . .