For the one of the first times in medical history, researchers and physicians at The Medical College of Wisconsin and Children’s Hospital of Wisconsin sequenced all the genes in a boy’s DNA to identify a previously-unknown mutation. The team was able not only to identify the mutation, but to develop a treatment plan using a cord blood transplant, and stop the course of the disease.
This accomplishment is published in the December 19, 2010 online edition of Genetics in Medicine http://journals.lww.com/geneticsinmedicine/pages/default.aspx Making a Definitive Diagnosis: Successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Lead authors are Elizabeth Worthey, Ph. D., and Alan N. Mayer, M.D. Ph.D. Collaborators at Children’s Hospital and the Medical College are David A. Margolis, M.D., James Verbsky, M.D., Ph.D., Howard J. Jacob, Ph. D., and David Dimmock, M.D.
At the age of 3, Nicholas Volker of Monona, Wisconsin, had already endured more than 100 surgeries, but was progressively getting sicker. His intestines continued to swell and more abscesses formed, and doctors concluded they were dealing with an unknown cause of disease.
Dr. Alan D. Mayer, assistant professor of Pediatrics at the Medical College, and pediatric gastroenterologist with Children’s Hospital, decided to look for the genetic source of the disease.
“Exhaustive efforts to reach a diagnosis revealed numerous abnormalities in Nick’s immune system, but none pointed to a specific disease,” Dr. Mayer explained. “So we decided the next logical step was to sequence his entire exome.”
Researchers examined all 20,000 of his genes looking for the cause of this rare disease. After three months poring over data, the researchers identified a unique mutation in one gene. They confirmed that mutation to be responsible for Nick’s previously-undocumented form of bowel disease, which is part of a broader XIAP deficiency.
The team then performed a blood cord transplant in June using stem cells from a matched, healthy donor. Five months later, Nick is home and eating a healthy diet for the first time.
“There has been no return of the bowel disease,” said Dr. David A. Margolis, the program director for the Blood and Marrow Transplant Program at Children’s Hospital, and associate professor of pediatrics at the Medical College. “At this point, he is a transplant recipient and his current treatment focuses on maintaining his health with the challenges posed by the transplant.”
The Medical College of Wisconsin and Children’s Hospital of Wisconsin are developing a new strategy as well as formal policies and procedures to guide the approach to future cases in which genetic sequencing will be used as a diagnostic tool.
“We are confident that genomic sequencing will have a growing role in establishing the correct diagnosis for patients and, most importantly, improving outcomes,” said Dr. Jacob, the Warren P. Knowles Professor of Molecular Genetics, director of the Medical College’s Human and Molecular Genetics Center and professor of physiology
About The Medical College of Wisconsin
The Medical College of Wisconsin is the state’s only private medical school and health sciences graduate school. Founded in 1893, it is dedicated to leadership and excellence in education, patient care, research and service. Approximately 1,200 students are enrolled in the Medical College’s medical school and graduate school programs A major national research center, it is the largest research institution in the Milwaukee metro area and second largest in Wisconsin. In FY 2009 -10, faculty received approximately $161 million in external support for research, teaching, training and related purposes, of which $148 million is for research. This total includes highly competitive research and training awards from the National Institutes of Health (NIH). Annually, College faculty direct or collaborate on more than 2,000 research studies, including clinical trials. Additionally, more than 1,200 faculty physicians provide care in virtually every specialty of medicine to approximately 390,000 patients annually.
About Children’s Hospital of Wisconsin
Children’s Hospital of Wisconsin, founded in 1894, is recognized as one of the leading pediatric health care centers in the United States. It is rated No. 3 in the nation by Parents magazine and named one of America’s Best Children’s Hospitals by U.S.News & World Report.
Children’s Hospital of Wisconsin is a Level I Pediatric Trauma Center verified by the American College of Surgeons. The hospital has been re-designated a Magnet hospital by the American Nurses Credentialing Center, a national honor that recognizes nursing excellence. Private, independent and not-for-profit, the hospital serves children and families from Wisconsin, the Upper Peninsula of Michigan, northern Illinois and beyond. Children’s Hospital is the flagship member of Children’s Hospital and Health System. In 2008, the health system invested more than $114 million back into the community to improve the health status of children. For more information, visit the website at www.chw.org.