title: [Mutational analysis of the PKD1 and PKD2 (type 1 and 2 dominant autosomal polycystic kidney) genes].
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. It is caused by mutations in at least two different genes: PKD1 and PKD2. The study of mutations in these genes is very difficult nowadays. In this study we have analyzed the non reiterated region of the PKD1 gene and all the exons and intron exon boundaries of the PKD2 gene. The technique used to study these genes have been single strand conformation analysis and heteroduplex. We have found 25 differences within the DNA sequence of the PKD1 gene with respect to the published sequence. Seven of these changes correspond to nonsense, missense, frameshifting and splicing mutations. The rest of changes correspond to polymorphisms or rare DNA variants. In the PKD2 gene we have identified 8 new mutations and one polymorphism. Six of these mutations are frameshifting, one is missense and the other one is a large deletion of the PKD2 gene. The rate of mutation detection within the PKD1 gene has been 4% and the rate for PKD2 has been 100%. We have not observed any correlation between genotype and phenotype either in the PKD1 nor in the PKD2 gene. The mutation analysis of ADPKD genes is very difficult, specially for the PKD1 gene. The rate of mutation detection is higher in the PKD2 gene but the global efficacy of the technique is very low as PKD2 represents only 15% of ADPKD patients. Nowadays linkage analysis is still the most useful technique for the molecular diagnosis of ADPKD patients.
authors.affiliation: Servicio de Nefrología, Hospital Clínic, Universidad de Barcelona, Madrid.
authors.forename: R
authors.initials: R
authors.lastname: Torra
authors.forename: C
authors.initials: C
authors.lastname: Badenas
authors.forename: L
authors.initials: L
authors.lastname: Pérez-Oller
authors.forename: J L
authors.initials: JL
authors.lastname: San Millán
authors.forename: D
authors.initials: D
authors.lastname: Tellería
authors.forename: X
authors.initials: X
authors.lastname: Estivill
authors.forename: A
authors.initials: A
authors.lastname: Darnell
mesh_terms: D004252:DNA Mutational Analysis; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D050396:TRPP Cation Channels
chemical_list: D008565:Membrane Proteins; D011506:Proteins; D050396:TRPP Cation Channels