The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein.
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.
Ward
Christopher J
CJ
Division of Nephrology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
Hogan
Marie C
MC
Rossetti
Sandro
S
Walker
Denise
D
Sneddon
Tam
T
Wang
Xiaofang
X
Kubly
Vicky
V
Cunningham
Julie M
JM
Bacallao
Robert
R
Ishibashi
Masahiko
M
Milliner
Dawn S
DS
Torres
Vicente E
VE
Harris
Peter C
PC
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
C451750:PKHD1 protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface