NIH Researchers Identify Genetic Cause of New Vascular Disease
Clinical researchers at the National Institutes of Health’s Undiagnosed Diseases Program (UDP) have identified the genetic cause of a rare and debilitating vascular disorder not previously explained in the medical literature. The adult-onset condition is associated with progressive and painful arterial calcification affecting the lower extremities, yet spares patients’ coronary arteries.
Akinso: Clinical researchers at the National Institutes of Health have identified the genetic cause of a rare and debilitating vascular disorder.
Gahl: We studied here a vascular disease that affected the large vessels of the lower extremity and also affected some of the joint capsules of our body.
Akinso: Dr. William Gahl is the National Human Genome Research Institute Clinical Director of the NIH Undiagnosed Disease Program. Gahl: And the way that it affected those vessels, there was calcification of those vessels and also some enlargement of the vessels and so blood wasn’t actually going through those vessels appropriately.
Akinso: Although symptoms of the disorder include leg and joint discomfort, medical evaluations of the patients ruled out rheumatoid arthritis or other joint-related problems. Genetic analyses performed by NIH researchers suggested a novel disorder and pinpointed the cause of the condition as mutations or variants, in the NT5E gene.
Gahl: The NT5E gene is like many other genes. It encodes a protein and the protein is called CD73 and that is what makes it special. So if you had a defect in that gene you’re not producing the CD73 protein and therefore there’s calcification that occurs and this whole mechanism is something that was found out because of individual patients who had this disorder and who’s gene mutation we found; again that gene was the NT5E gene.
Akinso: NIH clinical researchers examined members of two families with the arterial calcification disorder as part of the NIH Undiagnosed Disease Program. A third case has been identified outside the country. Dr. Gahl says vascular calcification often results from poor diet and lack of exercise, but the calcium buildup in arteries of these patients increases because the systems to inhibit calcium buildup are not working in their cells.
Gahl: We found that the gene was defective and we found that in three different families with this very, very unusual disorder. So the gene is defective and the gene product was not being made or it was being made improperly. Therefore it wasn’t functioning appropriately.
Akinso: Dr. Gahl adds this study shows that genomic tools are a powerful ally in the search to discover and understand rare diseases. The researchers refer to this condition as ACDC, or arterial calcification due to CD73 deficiency. For more information, visit www.nhgri.nih.gov. This is Wally Akinso at the National Institutes of Health Bethesda, Maryland.
About This Audio Report
Reporter: Wally Akinso
Sound Bite: Dr. William Gahl
Topic: vascular disease
Additional Info: NIH Researchers Identify Genetic Cause of New Vascular Disease