title: PKD1 and PKD2 mutations in Slovenian families with autosomal dominant polycystic kidney disease.
abstract: BACKGROUND
  Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder caused by mutations in at least two different loci. Prior to performing mutation screening, if DNA samples of sufficient number of family members are available, it is worthwhile to assign the gene involved in disease progression by the genetic linkage analysis.
  
  
  METHODS
  We collected samples from 36 Slovene ADPKD families and performed linkage analysis in 16 of them. Linkage was assessed by the use of microsatellite polymorphic markers, four in the case of PKD1 (KG8, AC2.5, CW3 and CW2) and five for PKD2 (D4S1534, D4S2929, D4S1542, D4S1563 and D4S423). Partial PKD1 mutation screening was undertaken by analysing exons 23 and 31-46 and PKD2 .
  
  
  RESULTS
  Lod scores indicated linkage to PKD1 in six families and to PKD2 in two families. One family was linked to none and in seven families linkage to both genes was possible. Partial PKD1 mutation screening was performed in 33 patients (including 20 patients from the families where linkage analysis could not be performed). We analysed PKD2 in 2 patients where lod scores indicated linkage to PKD2 and in 7 families where linkage to both genes was possible. We detected six mutations and eight polymorphisms in PKD1 and one mutation and three polymorphisms in PKD2.
  
  
  CONCLUSIONS
  In our study group of ADPKD patients we detected seven mutations: three frameshift, one missense, two nonsense and one putative splicing mutation. Three have been described previously and 4 are novel. Three newly described framesfift mutations in PKD1 seem to be associated with more severe clinical course of ADPKD. Previously described nonsense mutation in PKD2 seems to be associated with cysts in liver and milder clinical course.
authors.affiliation: Medical Centre for Molecular Biology, Institute of Biochemistry, Faculty of Medicine, Vrazov trg 2, 1000 Ljubljana, Slovenia. katjavouk@yahoo.co.uk
authors.forename: Katja
authors.initials: K
authors.lastname: Vouk
authors.forename: Lana
authors.initials: L
authors.lastname: Strmecki
authors.forename: Jitka
authors.initials: J
authors.lastname: Stekrova
authors.forename: Jana
authors.initials: J
authors.lastname: Reiterova
authors.forename: Matjaz
authors.initials: M
authors.lastname: Bidovec
authors.forename: Petra
authors.initials: P
authors.lastname: Hudler
authors.forename: Anton
authors.initials: A
authors.lastname: Kenig
authors.forename: Simona
authors.initials: S
authors.lastname: Jereb
authors.forename: Irena
authors.initials: I
authors.lastname: Zupanic-Pajnic
authors.forename: Joze
authors.initials: J
authors.lastname: Balazic
authors.forename: Guido
authors.initials: G
authors.lastname: Haarpaintner
authors.forename: Bostjan
authors.initials: B
authors.lastname: Leskovar
authors.forename: Anton
authors.initials: A
authors.lastname: Adamlje
authors.forename: Antun
authors.initials: A
authors.lastname: Skoflic
authors.forename: Reina
authors.initials: R
authors.lastname: Dovc
authors.forename: Radovan
authors.initials: R
authors.lastname: Hojs
authors.forename: Radovan
authors.initials: R
authors.lastname: Komel
mesh_terms: D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008126:Lod Score; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016891:Polycystic Kidney, Autosomal Dominant / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D017524:Slovenia; D050396:TRPP Cation Channels
chemical_list: D008565:Membrane Proteins; D011506:Proteins; D050396:TRPP Cation Channels