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Scientists identify cause of childhood kidney disease
Edward R. Winstead


Scientists have identified the gene responsible for an inherited liver and kidney disorder of childhood—a form of polycystic kidney disease (PKD). The researchers found the gene after first discovering that a similar disease occurs in rats. They then isolated the mutant rat gene and used this to locate the corresponding human gene, called PKHD1.

Detail of fibrocystin protein schematic. View larger

The gene's role in PKD was confirmed when the researchers detected mutations in PKHD1 in children with the recessive form of the disease. PKHD1 codes for a novel protein, called fibrocystin, and is expressed in the kidneys, liver and pancreas during fetal development, infancy and later childhood. Peter C. Harris, of the Mayo Clinic in Rochester, Minnesota, led the study. This is the first gene associated with the recessive form of PKD, which occurs when a child inherits two defective copies of PKHD1—one from each parent. Two other genes have previously been linked to a more common form of PKD.

The approximate location of PKHD1 on chromosome 6 has been known for about seven years. But success in the gene hunt came only after researchers discovered—and investigated—a new form of PKD in rats. To pinpoint the human gene on chromosome 6, researchers scanned the draft sequence of the human genome, which was not available when the region was first implicated in the disease.

"The precise pinpointing of the gene using the rat model with the greater genetic power inherent in an animal system were crucial to this study," the researchers write in Nature Genetics. "This project also highlights the importance of the Human Genome Project, as it provided sequence of the candidate region, and the use of gene-prediction programs for identifying potential" structures within the gene.

The autosomal recessive form of PKD is fatal in 30 percent of infants with the disease. Isolating the gene is an essential step toward the development of genetic screening tests. These tests will allow doctors to diagnose patients at risk for the disease by screening the PKHD1 gene for mutations.

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Ward, C.J. et al. The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein. Nat Genet. Published online February 4, 2002.

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