New research from the Simpson Lab

A brilliant new publication about UGDH variants is hot off the press in Matrix Biology.

This study, out of the Simpson Lab at North Carolina State University, examined three novel UGDH variants and concluded they are indeed pathogenic. This data will support the diagnosis of patients with those variants, but the study accomplished even more along the way.

Crucially, the team advanced the workflow for functionalizing variants of uncertain significance (VUS) by demonstrating a method of using cell culture models instead of patient-derived cells, which can be burdensome or impossible to acquire.

This advance eases the path for proving the pathogenicity of other uncharacterized VUS in UGDH, which will help many more families arrive at an accurate diagnosis.

The researchers also found that pathogenic variants may not always impact protein expression but can still profoundly impact development because of their uncontrolled behavior in low oxygen and/or low glucose conditions. This feature of the protein is hard to observe in structural models alone. Cellular models demonstrate it more dramatically.

So, through the lens of validating three novel variants, this research team contributed important findings to our fundamental understanding of the disease. The UGDH Founation is grateful to count Dr. Simpson as well as co-authors Dr. Barakat and Dr. Jamuar as members of our Scientific Advisory Board.