Rare diseases affect 30 million Americans, many of whom remain undiagnosed. Propionic acidemia is a genetic disorder with symptoms such as digestive issues and failure to thrive. While the Wisconsin newborn screening panel tests for the disorder and symptoms often emerge within the first few days of life, not all patients are properly diagnosed. One challenge in diagnosis is the more than 400 DNA variants that have not yet been specifically associated with disease symptoms. Our lab uses a minigene system to investigate a subset of these variants. While this system is effective in assessing individual variants, it is not high throughput. We are currently testing new approaches including altered processing of samples and Next Generation Sequencing technology in order to streamline and improve analysis. In the long term, we hope that identification of additional variants linked to propionic acidemia will allow for earlier diagnosis and that the pipeline may be applied to analysis of variants potentially associated with other rare genetic diseases.
