Dyskeratosis congenita (DC) is an inherited premature-aging syndrome that typically results in bone-marrow failure. Symptoms include abnormal skin pigmentation, abnormal or absent nails and white, pre-cancerous areas on the lips and in the eyes, mouth and other body openings. More than 80% of patients with DC develop bone-marrow failure, which leads to decreased production of all types of blood cells. Premature death is usually the result of bone marrow failure. Most cases of DC are caused by changes in the DKC1 gene on the X chromosome. DKC1 encodes a protein called dyskerin, which helps maintains chromosomes, in addition to its essential function of manufacturing protein synthesis machinery. A symptom-free mother carrying a DKC1 mutation has a 50% chance of transmitting it to a son who will develop the disease.
Using genetic and biochemical techniques, Dr. Judy Wong is working to determine the mechanisms of X-linked DC. There are more than thirty amino acid mutations of the dyskerin protein that are known to be associated with X-linked DC. Understanding the molecular events that give rise to X-linked DC will help predict how patients will be affected and assist in the development of genetic therapies. Dr. Wong plans to test the effectiveness of dyskerin gene replacement techniques in restoring normal activity in X-linked DC cells. Her work will also improve our understanding of how other physiological factors can compromise normal aging.