title: Cost-effective PKHD1 genetic testing for autosomal recessive polycystic kidney disease.
abstract: BACKGROUND
  Genetic diagnosis of autosomal recessive polycystic kidney disease (ARPKD) is challenging due to the length and allelic heterogeneity of the PKHD1 gene. Mutations appear to be clustered at specific exons, depending on the geographic origin of the patient. We aimed to identify the PKHD1 exons most likely mutated in Spanish ARPKD patients.
  
  
  METHODS
  Mutation analysis was performed in 50 ARPKD probands and nine ARPKD-suspicious patients by sequencing PKHD1 exons arranged by their reported mutation frequency. Haplotypes containing the most frequent mutations were analyzed. Other PKD genes (HNF1B, PKD1, PKD2) were sequenced in PKHD1-negative cases.
  
  
  RESULTS
  Thirty-six different mutations (concentrated in 24 PKHD1 exons) were detected, giving a mutation detection rate of 86%. The screening of five exons (58, 32, 34, 36, 37) yielded a 54% chance of detecting one mutation; the screening of nine additional exons (3, 9, 39, 61, 5, 22, 26, 41, 57) increased the chance to 76%. The c.9689delA mutation was present in 17 (34%) patients, all of whom shared the same haplotype. Two HNF1B mutations and one PKD1 variant were detected in negative cases.
  
  
  CONCLUSIONS
  Establishing a PKHD1 exon mutation profile in a specific population and starting the analysis with the most likely mutated exons might significantly enhance the efficacy of genetic testing in ARPKD. Analysis of other PKD genes might be considered, especially in suspicious cases.
authors.affiliation: Molecular Biology Laboratory, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, REDinREN, Instituto de Investigación Carlos III, C/Cartagena, 340-350, 08025, Barcelona, Spain.
authors.forename: Paola
authors.initials: P
authors.lastname: Krall
authors.forename: Cristina
authors.initials: C
authors.lastname: Pineda
authors.forename: Patricia
authors.initials: P
authors.lastname: Ruiz
authors.forename: Laia
authors.initials: L
authors.lastname: Ejarque
authors.forename: Teresa
authors.initials: T
authors.lastname: Vendrell
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Camacho
authors.forename: Santiago
authors.initials: S
authors.lastname: Mendizábal
authors.forename: Artur
authors.initials: A
authors.lastname: Oliver
authors.forename: José
authors.initials: J
authors.lastname: Ballarín
authors.forename: Roser
authors.initials: R
authors.lastname: Torra
authors.forename: Elisabet
authors.initials: E
authors.lastname: Ars
mesh_terms: D003362:Cost-Benefit Analysis; D004252:DNA Mutational Analysis / Q000379:methods*; D005091:Exons / Q000235:genetics; D005820:Genetic Testing / Q000191:economics*; D006239:Haplotypes; D006801:Humans; D009154:Mutation; D017044:Polycystic Kidney, Autosomal Recessive / Q000175:diagnosis* / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: C451750:PKHD1 protein, human; D011956:Receptors, Cell Surface