Background: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic diseases of human. Traditionally, ADPKD is diagnosed by ultrasonography, computed tomography (CT) or magnetic resonance imaging (MRI) of kidneys for the presence of renal cysts. Individuals who carry the defective gene but have not yet developed cysts in kidney may not be diagnosed. Genetic analysis reveals it to be caused mostly by a single-gene disorder of a genetic locus, designated PKD1. Recently, the genetic locus involving PKD1 has been identified on chromosome 16p13.3, and has been cloned and completely sequenced.
Methods: A pair of primers, KG8-CA, located between D16S84 and D16S125, was selected and synthesized for the polymerase chain reaction (PCR) to identify individuals who may carry the defective locus. The sequence of KG8-CA primers, was 5'-CTCCCAGGGTGGAGGAAGGTG-3' and 5'-GCAGGCACAGCCAGCTCCGAG-3'. PCR products were analyzed in denaturing condition, using gel containing 8% acrylamide and 7M urea. Autoradiography was carried out to interpret the results.
Results: Four Chinese families with history of ADPKD showed different DNA patterns in individuals with ADPKD and in normal individuals. Among the members in four families with history of ADPKD, every individual shared a common DNA band, suggesting that this band was derived from normal PKD1 allele. On the other hand, individuals diagnosed to have ADPKD showed one or two additional DNA bands which migrated differently from the common DNA band and should therefore be derived from defective ADPKD allele. Previous studies have shown that the ADPKD allele is highly polymorphic, as was evident in these family studies.
Conclusions: Among the members from these four families, some were clinically normal and had DNA pattern that was typical to patients with ADPKD. These individuals might carry the defective PKD1 allele but have not yet developed the ADPKD symptoms. Therefore, the method described in this study has diagnostic values for pre-symptomatic individuals as well as for patients already diagnosed with ADPKD.