Mutational analysis of PKD1 and PKD2 genes (autosomal dominant polycystic disease type 1 and 2)

Autosomal dominant polycystic kidney disease (ADPKD) is the most common her editary 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 diffic ult nowadays. In this study we have analyzed the non reiterated region of the PKD1 gene a nd all the exons and intron exon boundaries of the PKD2 gene. The technique used to study these genes have been single strand conformation analysis an d 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 non sense, 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 th e 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 P KD1 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% o f ADPKD patients. Nowadays linkage analysis is still the most useful techni que for the molecular diagnosis of ADPKD patients.