ANP mutation causes reduced proteolysis

Background A heterozygous frameshift (fs) mutation causing a 12 amino acid extension to the C-terminus of atrial natriuretic peptide (ANP) was recently genetically linked to patients with familial atrial fibrillation [1]. The frameshift product (fsANP), but not wild type ANP (wtANP), was elevated in the serum of affected patients, but the molecular basis for the elevated peptide concentrations was not determined. Here, we measured the ability of fsANP to interact with natriuretic peptide receptors and to be proteolytically degraded.