Journal Article

A Novel Channelopathy in Pulmonary Arterial Hypertension

Austin, Eric D, Girerd, Barbara, Humbert, Marc, Ma, Lijiang, Sampson, Kevin S, Chung, Wendy K, Montani, David, Loyd, James E, Eyries, Mélanie, Germain, Marine, Kass, Robert S, Borczuk, Alain, Trégouët, David-Alexandre, Roman-Campos, Danilo, Soubrier, Florent, Rosenzweig, Erika Berman

2013

Overview

In a family with pulmonary arterial hypertension, whole-exome sequencing led to identification of a mutation in the potassium-channel gene KCNK3 . Additional mutations resulting in loss of function of the channel were found in other families and in patients with idiopathic disease. Pulmonary arterial hypertension is a rare disease that is characterized by increased pulmonary-artery pressure in the absence of common causes of pulmonary hypertension, such as chronic heart, lung, or thromboembolic disease. 1 Before the advent of novel therapies, patients with idiopathic or familial pulmonary arterial hypertension had an estimated median survival of 2.8 years, with 1-year, 3-year, and 5-year survival rates of 68%, 48%, and 34%, respectively. 2 However, despite progress in treatment, pulmonary arterial hypertension remains a progressive, fatal disease. The clinical presentation can be nonspecific, and patients often receive a diagnosis late in their clinical course. The cause of pulmonary . . .

• Publisher: Massachusetts Medical Society
• Subject: Amino Acid Sequence / Biological and medical sciences / Bone morphogenetic protein receptor type II / Calcium channels (voltage-gated) / Channelopathies - drug therapy / Channelopathies - genetics / Channelopathy / Chlorobenzoates - therapeutic use / Cinnamates - therapeutic use / Drug therapy / Exome / Familial Primary Pulmonary Hypertension / Female / General aspects / Genes / Genetic Predisposition to Disease / Heterozygote / Humans / Hypertension / Hypertension, Pulmonary - drug therapy / Hypertension, Pulmonary - genetics / Lung - pathology / Male / Medical sciences / Missense mutation / Molecular Sequence Data / Mutation / Mutation, Missense / Nerve Tissue Proteins - chemistry / Nerve Tissue Proteins - genetics / Nerve Tissue Proteins - physiology / ortho-Aminobenzoates - therapeutic use / Pedigree / Phospholipase / Pneumology / Potassium channels / Potassium Channels, Tandem Pore Domain - chemistry / Potassium Channels, Tandem Pore Domain - genetics / Potassium Channels, Tandem Pore Domain - physiology / Proteins / Pulmonary hypertension / Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases / Sequence Analysis, DNA