The PKD1 gene product

We would like to bring to your attention a report that has significant implications for an autosomal dominant polycystic kidney disease study that was reported in the April issue of Nature Medicine. This study described the characterization and localization of an extracellular matrix protein using antibodies raised against a decapeptide from the predicted extreme COOH-terminal domain of the PKD1 gene product. The American Polycystic Kidney Disease Consortium has identified an important difference between their sequence and that previously published; a two-base pair insertion results in the replacement of the originally predicted 92 COOH-terminal residues with 12 novel residues. This sequence difference has been found in two cloned genomic templates and one cDNA template and has been confirmed using allele-specific oligonucleotides and PCR products derived from the genomic DNA of nine individuals. The European Polycystic Kidney Disease Consortium has also re-analysed the original sequence and confirmed the presence of the two-base pair insertion. We therefore conclude that there are currently no data supporting the presence of the originally published COOH terminal peptide sequence within the final PKD1 gene product. It is clear, therefore, that the relationship between the PKD1 gene product to the extracellular matrix protein identified with these anti-peptide antibodies is uncertain and should be viewed with caution.