Feb. 12, 2002 ROCHESTER, MINN. - Researchers at Mayo Clinic have identified the gene causing an inherited form of childhood kidney disease associated with renal failure and neonatal death. The discovery may improve prospects for gene testing and diagnosis of this life-threatening disease.
The results of the Mayo Clinic study are published in the March issue of Nature Genetics.
Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common childhood diseases of the kidneys. ARPKD, also known as infantile PKD, affects one in 20,000 Americans. The disease results in the development of multiple fluid-filled cysts in the kidney, fibrosis in the liver and often poor lung development and neonatal death.
"Identifying the causative gene is a major step forward, as the progression of the disease can now be studied. It improves the prospects for gene-based diagnostics," says Peter C. Harris, Ph.D., Mayo Clinic nephrologist and the lead researcher in the study.
Improved respiratory treatment has increased newborn survival, but roughly 30 percent of affected babies still die in infancy. Renal disease is usually evident in the neonate. However, when ARPKD appears later in childhood, it is usually associated with less massive renal enlargement and more variability in cyst size. Approximately 50 percent of affected babies who survive the neonatal period progress to end-stage renal disease (ESRD) within 10 years. About 45 percent of infants with ARPKD also have liver disease, which is often a major feature in older children.
Two genes have been identified for the more common, dominant form of PKD. The genetic cause of the recessive type, inherited only when both parents carry an abnormal copy of the disease gene, was more difficult to isolate. In 1994, a German group narrowed the area of the disease gene to a region on chromosome 6. Dr. Harris and colleagues at Mayo Clinic were able to identify the gene by first finding a gene that causes a similar disease in rats. Dr. Harris’ group analyzed a rat with a similar form of PKD that arose in a breeding colony in Japan. Identifying the gene in the rat, and analyzing ARPKD patients, led the researchers to realize that the human equivalent of the rat gene was the one that was abnormal in this disease.
Progress on the Human Genome Project, which sequenced the candidate region on chromosome 6, aided identification of the gene. The gene is very large, covering almost 500,000 DNA bases (an average gene spans about 30,000 bases) and is predicted to encode a large new protein, termed fibrocystin. As yet the normal role of this protein is unknown, but identifying the basic defect in this disorder is a first step to understanding its pathogenesis.
This research was funded in part by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.
Other social bookmarking and sharing tools:
The above story is reprinted from materials provided by Mayo Clinic.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Note: If no author is given, the source is cited instead.