Use of a DNA probe in the diagnosis of adult polycystic kidney disease.

Adult polycystic kidney disease (APKD) is one of the most common inherited diseases in man. A diagnosis based on the demonstration of renal cysts with ultrasonography or computerised tomography may be inconclusive in early adulthood, the crucial years before child-bearing is complete. Here we describe the improved diagnostic probability that is possible using genetic linkage studies. A 24-year-old woman, whose father and younger sister were affected by APKD, was demonstrated to have a single cyst in each kidney. These findings were insufficient for a diagnosis of APKD and for this reason genetic linkage studies were undertaken. DNA was extracted from peripheral blood leukocytes from the presenting individual, and her immediate and extended family; the DNA was cut with the restriction enzyme PvuII, electrophoresed in a 0.7% agarose gel and blotted onto nitrocellulose before probing with a 32P-labelled 4 kb fragment. This contained DNA from the hypervariable region (3' hypervariable region, 3'HVR) that is linked to the gene for APKD on the short arm of chromosome 16 and has been used in other family studies by Reeders et al. We correlated the findings on Southern blotting with ultrasound evidence of APKD and found that the disease segregated with a 7.0 kb fragment in the presenting individual's father and sister. She was shown to have inherited this allele also; the use of this technique thus increased the probability of her having APKD from 50% to 96.5%.