The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein

Christopher J. Ward, Marie C. Hogan, Sandro Rossetti, Denise Walker, Tam Sneddon, Xiaofang Wang, Vicky Kubly, Julie M. Cunningham, Robert Bacallao, Masahiko Ishibashi, Dawn S. Milliner, Vicente E. Torres, Peter C. Harris

Research output: Contribution to journalArticle

523 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)259-269
Number of pages11
JournalNature genetics
Volume30
Issue number3
DOIs
StatePublished - Mar 2002

ASJC Scopus subject areas

  • Genetics

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    Ward, C. J., Hogan, M. C., Rossetti, S., Walker, D., Sneddon, T., Wang, X., Kubly, V., Cunningham, J. M., Bacallao, R., Ishibashi, M., Milliner, D. S., Torres, V. E., & Harris, P. C. (2002). The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein. Nature genetics, 30(3), 259-269. https://doi.org/10.1038/ng833