title: The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein.
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.
authors.affiliation: Division of Nephrology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ward
authors.forename: Marie C
authors.initials: MC
authors.lastname: Hogan
authors.forename: Sandro
authors.initials: S
authors.lastname: Rossetti
authors.forename: Denise
authors.initials: D
authors.lastname: Walker
authors.forename: Tam
authors.initials: T
authors.lastname: Sneddon
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wang
authors.forename: Vicky
authors.initials: V
authors.lastname: Kubly
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Robert
authors.initials: R
authors.lastname: Bacallao
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ishibashi
authors.forename: Dawn S
authors.initials: DS
authors.lastname: Milliner
authors.forename: Vicente E
authors.initials: VE
authors.lastname: Torres
authors.forename: Peter C
authors.initials: PC
authors.lastname: Harris
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D017044:Polycystic Kidney, Autosomal Recessive / Q000175:diagnosis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: C451750:PKHD1 protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface