Background: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic diseases in humans, affecting 1 out of 1000 individuals. At least three different genes are involved in this disease. The search for mutations in PKD1 is complicated because most of the transcript is encoded by a genomic region reiterated more proximally on chromosome 16, and no prevalent mutation has been reported.
Methods: We have screened DNA from exon 43 through exon 46 and intron 40 of the PKD1 sequence by single-stranded conformational polymorphism (SSCP) analysis in 175 ADPKD patients.
Results: We have found 25 differences with respect to the reported PKD1 DNA sequence, seven of which are mutations (Q4041X, Q4124X, IVS44-1G-->C, IVS45-1G-->A, 12801del28, R4275W, and Q4224P). We found different phenotypical expressions of the same mutation in the families studied. We have detected several common polymorphisms, and some of them cosegregate, suggesting a common origin of these alleles in PKD1.
Conclusions: The detection of only seven mutations in 175 unrelated ADPKD patients for this region of the PKD1 analyzed suggests that mutations could be widespread throughout all of the gene and that a prevalent mutation is not expected to occur. The identified PKD1 missense mutations may help to refine critical regions of the protein. Until a quicker and more sensitive method for the detection of mutations becomes available, linkage studies will continue to be the basis for the molecular diagnosis of ADPKD families.