title: Family history of renal disease severity predicts the mutated gene in ADPKD.
abstract: Mutations of PKD1 and PKD2 account for 85 and 15% of cases of autosomal dominant polycystic kidney disease (ADPKD), respectively. Clinically, PKD1 is more severe than PKD2, with a median age at ESRD of 53.4 versus 72.7 yr. In this study, we explored whether a family history of renal disease severity predicts the mutated gene in ADPKD. We examined the renal function (estimated GFR and age at ESRD) of 484 affected members from 90 families who had ADPKD and whose underlying genotype was known. We found that the presence of at least one affected family member who developed ESRD at age < or =55 was highly predictive of a PKD1 mutation (positive predictive value 100%; sensitivity 72%). In contrast, the presence of at least one affected family member who continued to have sufficient renal function or developed ESRD at age >70 was highly predictive of a PKD2 mutation (positive predictive value 100%; sensitivity 74%). These data suggest that close attention to the family history of renal disease severity in ADPKD may provide a simple means of predicting the mutated gene, which has prognostic implications.
authors.affiliation: Division of Nephrology and Genomic Medicine, Department of Medicine, University of Toronto and University Health Network, Toronto, Ontario, Canada.
authors.forename: Moumita
authors.initials: M
authors.lastname: Barua
authors.forename: Onur
authors.initials: O
authors.lastname: Cil
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Paterson
authors.forename: Kairon
authors.initials: K
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: He
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dicks
authors.forename: Patrick
authors.initials: P
authors.lastname: Parfrey
authors.forename: York
authors.initials: Y
authors.lastname: Pei
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000209:etiology*; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000235:genetics*; D050396:TRPP Cation Channels / Q000235:genetics*; D055815:Young Adult
chemical_list: D050396:TRPP Cation Channels