Kansas City, Mo. (February 6, 2002) – Researchers at the Mayo Clinic have identified and fully characterized the gene that causes autosomal recessive polycystic kidney disease (ARPKD), raising hopes of a treatment and eventual cure for infants born with ARPKD. The Polycystic Kidney Disease (PKD) Foundation provided grants that led to the promising discovery of the PKHD1 gene, an effort aided by earlier work done at the Human Genome Project. The March 2002 issue of Nature Genetics will feature this breakthrough.
ARPKD is one of a group of polycystic kidney diseases that together make up the world’s most common life-threatening genetic disease, affecting 600,000 children and adults in the United States and 12.5 million people worldwide. In the U.S., more people have PKD than the combined number of those who have cystic fibrosis, muscular dystrophy, Down’s syndrome, hemophilia, sickle cell anemia and Huntington’s disease. The disease affects people equally irrespective of age, race, gender, ethnicity, geographic location or socioeconomic status.
ARPKD, often referred to as “infantile PKD,” is a particularly lethal form of PKD resulting in the development of multiple fluid-filled cysts in the kidney and fibrosis in the liver. The disease is often associated with poor lung development and infant death. There is currently no treatment or cure for ARPKD, but the discovery of the ARPKD gene now provides researchers with a genetic “road map” for a functional understanding of how PKD progresses, and “paves the way” for gene testing, more conclusive diagnosis, and treatments to retard development of the disease.
“Identifying the causative gene is a major step forward as the basic defect and progression of the disease can now be studied,” said Peter C. Harris, Ph.D., of the Mayo Clinic and the lead researcher in the study. “The identification of PKHD1 eventually will allow expectant parents to learn through confidential testing if their babies have a genetic pre-disposition for the disease. This will arm people at risk for ARPKD with information to help them make educated decisions affecting themselves and their families.”
The physical, psychological and financial effects ARPKD has on the entire family are devastating. Parents who each carry one abnormal ARPKD gene have a one-in-four chance that every conception will result in a child with ARPKD. The vast majority of those who have PKD develop kidney failure, costing U.S. taxpayers an estimated annual $2 billion for costs related to dialysis, kidney transplantation and related therapies.
“Our first child, Ryan, died of ARPKD shortly after birth,” said Diane Keating of suburban Chicago. “My husband and I had no idea we were even at risk to have a child with kidney disease. Then Austin, our third child, was diagnosed with ARPKD when I was in my thirty-second week of pregnancy.” Mrs. Keating later donated one of her kidneys to Austin to save her now five-year old son’s life. “Austin has shown us how to meet these battles and fight this disease, and now we look forward to treatments and a cure.”
“Knowing the gene defect will result in a better understanding of the disease, leading eventually to effective therapies,” added Dr. Harris. “This discovery gives PKD researchers, patients and their families hope against a disease that was previously poorly understood.”
The mission of the PKD Foundation, an international not-for-profit organization based in Kansas City, Mo., is to seek a treatment and cure for PKD. It is the only organization worldwide solely devoted to programs of PKD research, patient education, public awareness and advocacy for PKD families. Since 1984, the PKD Foundation has funded $10 million dollars of PKD research. More information about PKD and the PKD Foundation can be found at www.pkdcure.org or by calling 800-PKD-CURE (753-2873).
Editor’s Note: Francis Collins, M.D., Ph.D., Director of the National Human Genome Research Institute at the National Institutes of Health commented on the discovery of the gene PKHD1:
“The identification of the gene for ARPKD is a tour de force of modern molecular genetics. The team that achieved this goal brought to bear on this problem the powerful genomics toolbox now available for such studies. It is gratifying to see that the publicly available sequence of the human genome played such an important role in this discovery. With the identification of the responsible gene and the characterization of a rat model of the disease, rapid progress in understanding ARPKD can be anticipated. The ARPKD gene identification is a marvelous piece of scientific sleuthing.”
Journal
Nature Genetics