Loss-of-Function ABCC8 Mutations in Pulmonary Arterial Hypertension.

ABSTRACT:

Background

In pulmonary arterial hypertension (PAH), pathological changes in pulmonary arterioles progressively raise pulmonary artery pressure and increase pulmonary vascular resistance, leading to right heart failure and high mortality rates. Recently, the first potassium channelopathy in PAH, because of mutations in KCNK3, was identified as a genetic cause and pharmacological target.

Methods

Exome sequencing was performed to identify novel genes in a cohort of 99 pediatric and 134 adult-onset group I PAH patients. Novel rare variants in the gene identified were independently identified in a cohort of 680 adult-onset patients. Variants were expressed in COS cells and function assessed by patch-clamp and rubidium flux analysis.

Results

We identified a de novo novel h

SUBMITTER: Bohnen MS 

PROVIDER: S-EPMC6206877 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature