title: Clinical utility of PKD2 mutation testing in a polycystic kidney disease cohort attending a specialist nephrology out-patient clinic.
abstract: BACKGROUND
  ADPKD affects approximately 1:1000 of the worldwide population. It is caused by mutations in two genes, PKD1 and PKD2. Although allelic variation has some influence on disease severity, genic effects are strong, with PKD2 mutations predicting later onset of ESRF by up to 20 years. We therefore screened a cohort of ADPKD patients attending a nephrology out-patient clinic for PKD2 mutations, to identify factors that can be used to offer targeted gene testing and to provide patients with improved prognostic information.
  
  
  METHODS
  142 consecutive individuals presenting to a hospital nephrology out-patient service with a diagnosis of ADPKD and CKD stage 4 or less were screened for mutations in PKD2, following clinical evaluation and provision of a detailed family history (FH).
  
  
  RESULTS
  PKD2 mutations were identified in one fifth of cases. 12% of non-PKD2 patients progressed to ESRF during this study whilst none with a PKD2 mutation did (median 38.5 months of follow-up, range 16-88 months, p < 0.03). A significant difference was found in age at ESRF of affected family members (non-PKD2 vs. PKD2, 54 yrs vs. 65 yrs; p < 0.0001). No PKD2 mutations were identified in patients with a FH of ESRF occurring before age 50 yrs, whereas a PKD2 mutation was predicted by a positive FH without ESRF.
  
  
  CONCLUSIONS
  PKD2 testing has a clinically significant detection rate in the pre-ESRF population. It did not accurately distinguish those individuals with milder renal disease defined by stage of CKD but did identify a group less likely to progress to ESRF. When used with detailed FH, it offers useful prognostic information for individuals and their families. It can therefore be offered to all but those whose relatives have developed ESRF before age 50.
authors.affiliation: Academic Department of Medical Genetics, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0SP, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Robinson
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Hiemstra
authors.forename: Deborah
authors.initials: D
authors.lastname: Spencer
authors.forename: Sarah
authors.initials: S
authors.lastname: Waller
authors.forename: Laura
authors.initials: L
authors.lastname: Daboo
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Karet Frankl
authors.forename: Richard N
authors.initials: RN
authors.lastname: Sandford
mesh_terms: D000328:Adult; D000368:Aged; D000554:Ambulatory Care Facilities / Q000706:statistics & numerical data*; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009398:Nephrology / Q000706:statistics & numerical data; D007690:Polycystic Kidney Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D012307:Risk Factors; D050396:TRPP Cation Channels / Q000235:genetics*; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D050396:TRPP Cation Channels