OMRF researchers identify gene mutation

Published: Wednesday, September 20, 2017 By: Journal Record Staff Source: The Journal Record

Scientists at the Oklahoma Medical Research Foundation have discovered how mutations in one specific gene can cause two distinct and rare diseases.

OMRF researcher Lorin Olson studies a protein signal called platelet-derived growth factor, which plays a key role in the body’s ability to repair wounds. But too much PDGF promotes fibrosis and inflammation, making proper balance key. Olson’s research focuses on understanding how PDGF works.

In a new paper published in the journal Genes and Development, Olson and his team have shown how too much PDGF causes disease. Specifically, they’ve found how mutations in PDGF receptor beta (PDGFRB) can trigger two rare diseases, Penttinen syndrome and Kosaki overgrowth syndrome.

“Typically, mutations in the same gene are predicted to have the same outcome,” said Olson. “So we were puzzled by reports that two unique diseases were coming from the same mutant gene.”

Using mouse models, Olson was able to show that the diseases caused by PDGFRB mutations are largely determined by a modifying gene called STAT1. When STAT1 was present along with a PDGFRB mutation, it led to the appearance of premature aging in mice, similar to what happens in Penttinen syndrome in humans. On the other hand, if a PDGFRB mutation occurred in the absence of STAT1, they saw overgrowth in mice similar to symptoms of Kosaki overgrowth syndrome.

As a result, Olson and his lab were able to pinpoint STAT1 as a determining factor in which disease results from mutations in the PDGFRB gene.

Olson came to OMRF from the Mt. Sinai School of Medicine in New York, New York, in 2010. He received his Ph.D. from the University of California, San Diego, and now is an associate member in OMRF’s Cardiovascular Biology Research Program.

Other OMRF researchers who contributed to the findings were Shayna Medley, Jang Kim, Chengyi Sun, Hae Ryong Kwon, Hiromi Sakashita, Yair Pincu, Longbiao Yao and Timothy Griffin. Other former OMRF scientists involved in the work were Chaoyong He and Danielle Eppard.

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