Nature Genetics30, 259 - 269 (2002)
Published online: 4 February 2002; | doi:10.1038/ng833
The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein
Christopher J. Ward1, Marie C. Hogan1, Sandro Rossetti1, Denise Walker1, Tam Sneddon1, Xiaofang Wang1, Vicky Kubly1, Julie M. Cunningham2, Robert Bacallao3, Masahiko Ishibashi4, Dawn S. Milliner1, Vicente E. Torres1
& Peter C. Harris1
1
Division of Nephrology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
2
Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
3
Department of Medicine, Indiana University Medical Center, Indianapolis, Indiana 46202, USA.
Autosomal recessive polycystic kidney disease (ARPKD) is characterized by dilation of collecting ducts and by biliary dysgenesis and is an important cause of renal- and liver-related morbidity and mortality. Genetic analysis of a rat with recessive polycystic kidney disease revealed an orthologous relationship between the rat locus and the ARPKD region in humans; a candidate gene was identified. A mutation was characterized in the rat and screening the 66 coding exons of the human ortholog (PKHD1) in 14 probands with ARPKD revealed 6 truncating and 12 missense mutations; 8 of the affected individuals were compound heterozygotes. The PKHD1 transcript, approximately 16 kb long, is expressed in adult and fetal kidney, liver and pancreas and is predicted to encode a large novel protein, fibrocystin, with multiple copies of a domain shared with plexins and transcription factors. Fibrocystin may be a receptor protein that acts in collecting-duct and biliary differentiation.
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