Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC

Mutation in Potassium Channel Gene Linked to Rare Form of Pulmonary Hypertension

By BiotechDaily International staff writers
Posted on 08 Aug 2013
Image: Cross section of a potassium channel in a smooth muscle cell of the pulmonary artery. A recent study has identified six new mutations in a gene called KCNK3 that can interfere with the function of potassium channels and lead to pulmonary hypertension. The mutations are depicted in color at the locations where they exert their effects (Photo courtesy of Columbia University Medical Center).
Image: Cross section of a potassium channel in a smooth muscle cell of the pulmonary artery. A recent study has identified six new mutations in a gene called KCNK3 that can interfere with the function of potassium channels and lead to pulmonary hypertension. The mutations are depicted in color at the locations where they exert their effects (Photo courtesy of Columbia University Medical Center).
A mutation in a gene that encodes a potassium channel protein has been linked to development of the rare disease idiopathic pulmonary arterial hypertension (PAH).

PAH, a rare fatal disease with an incidence of about two to three cases per million of population per year, is characterized by high blood pressure in the lungs that eventually leads to coronary hypertrophy and death. Current there is no cure or effective treatment for PAH, and most PAH patients die within five to seven years of diagnosis.

To gain a better understanding for the underlying genetic cause behind PAH, investigators at the Columbia University Medical Center (New York, NY, USA) studied a family in which multiple members had PAH without identifiable mutations in any of the genes known to be associated with the disease, including BMPR2, ALK1, ENG, SMAD9, and CAV1. Three family members were studied with whole-exome sequencing. Additional patients with familial or idiopathic PAH were screened for the mutations in the gene that was identified on whole-exome sequencing.

The investigators reported in the July 15, 2013, online edition of the New England Journal of Medicine (NEJM) that they had identified a novel heterozygous missense variant in KCNK3 (the gene encoding potassium channel subfamily K, member 3) as a disease-causing candidate gene in the family. Five additional heterozygous missense variants in KCNK3 were independently identified in 92 unrelated patients with familial PAH and 230 patients with idiopathic PAH.

Computer models predicted that all six novel variants would be damaging to channel protein function, and these predictions were confirmed by electrophysiological studies of the channel that showed that all the missense mutations resulted in loss of function. The reduction in potassium-channel current caused by the mutations in KCNK3 could be reversed in cell cultures by treatment with a phospholipase inhibitor, the candidate drug ONO-RS-082.

“We were surprised to learn that KCNK3 appears to play a role in the function of potassium channels in the pulmonary artery,” said senior author Dr. Wendy K. Chung, associate professor of pediatrics and medicine at Columbia University Medical Center. “No one had suspected that this mechanism might be associated with PAH. The most exciting thing about our study is not that we have identified a new gene involved in pulmonary hypertension, but that we have found a drug that can rescue some mutations. In genetics, it is common to identify a gene that is the source of a disease. However, it is relatively rare to find potential treatments for genetic diseases.”

“KCNK3 mutations are a rare cause of PAH, so I do not want to oversell our findings,” said Dr. Chung. “Still, it is exciting that we have found a mechanism that can lead to the disease that is a new, druggable target. It is also possible that targeting KCNK3 may be beneficial for patients who have PAH independent of their KCNK3 genetic status.”

Related Links:

Columbia University Medical Center



Channels

Drug Discovery

view channel
Image: Molecular model of the protein Saposin C (Photo courtesy of Wikimedia Commons).

Nanovesicles Kill Human Lung Cancer Cells in Culture and in a Mouse Xenograft Model

Nanovesicles assembled from the protein Saposin C (SapC) and the phospholipid dioleoylphosphatidylserine (DOPS) were shown to be potent inhibitors of lung cancer cells in culture and in a mouse xenograft model.... Read more

Biochemistry

view channel

Possible New Target Found for Treating Brain Inflammation

Scientists have identified an enzyme that produces a class of inflammatory lipid molecules in the brain. Abnormally high levels of these molecules appear to cause a rare inherited eurodegenerative disorder, and that disorder now may be treatable if researchers can develop suitable drug candidates that suppress this enzyme.... Read more

Lab Technologies

view channel
Image: The FLUOVIEW FVMPE-RS Gantry microscope (Photo courtesy of Olympus).

New Multiphoton Laser Scanning Microscope Configurations Expand Research Potential

Two new configurations of a state-of-the-art multiphoton laser scanning microscope extend the usefulness of the instrument for examining rapidly occurring biological events and for obtaining images from... Read more

Business

view channel

Roche Acquires Signature Diagnostics to Advance Translational Research

Roche (Basel, Switzerland) will advance translational research for next generation sequencing (NGS) diagnostics by leveraging the unique expertise of Signature Diagnostics AG (Potsdam, Germany) in biobanks and development of novel NGS diagnostic assays. Signature Diagnostics is a privately held translational oncology... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.