title: Genetics and phenotypic characteristics of autosomal dominant polycystic kidney disease in Finns.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, leading to renal insufficiency and renal transplantation. Mutation screening in the major gene for ADPKD, the polycystic kidney disease type 1 (PKD1) gene, has often been incomplete because of multiple homologous copies of this gene elsewhere on chromosome 16. Furthermore, there are only a few studies investigating genotype-phenotype correlations in patients with ADPKD. In this study, we screened the entire coding region of the PKD1 and PKD2 genes in 17 Finnish families with ADPKD via long-range polymerase chain reaction, single-strand conformation polymorphism analysis, and direct sequencing. We were able to identify mutations co-segregating with ADPKD in all 16 families linked to PKD1 by haplotype analysis. Of these mutations, six were insertions/deletions, five nonsense mutations, and five missense mutations. In the only PKD2-linked family, we found a missense mutation, R322Q. With the exception of one mutation (L845S in PKD1), all mutations were novel. Mutations and their location did not have a strong correlation with the phenotype with the exception of subarachnoidal hemorrhage or brain aneurysm, where mutations were located more often at the 5' end of the PKD1 gene than at the 3' end of the PKD1 gene.
authors.affiliation: Department of Medicine, University of Kuopio, P.O. Box 1777, 70211 Kuopio, Finland.
authors.forename: Paula
authors.initials: P
authors.lastname: Peltola
authors.forename: Anne
authors.initials: A
authors.lastname: Lumiaho
authors.forename: Raija
authors.initials: R
authors.lastname: Miettinen
authors.forename: Jussi
authors.initials: J
authors.lastname: Pihlajamäki
authors.forename: Richard
authors.initials: R
authors.lastname: Sandford
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
mesh_terms: D000328:Adult; D017668:Age of Onset; D000595:Amino Acid Sequence; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D050396:TRPP Cation Channels
chemical_list: D008565:Membrane Proteins; D011506:Proteins; D050396:TRPP Cation Channels