Background. Autosomal dominant polycystic kidney disease (ADPKD) is genetic
ally heterogeneous, with at least three chromosomal loci accounting for the
disease. Mutations in the PKD2 gene on the long arm of chromosome 4 are ex
pected to be responsible for approximately 15% of cases of ADPKD.
Methods. We report a systematic screening for mutations covering the 15 exo
ns of the PKD2 gene in eight unrelated families with ADPKD type 2, using th
e heteroduplex technique.
Results. Seven novel mutations were identified and characterized that, toge
ther with the previously described changes, amount to a detection rate of 8
5% in the population studied. The newly described mutations are two nonsens
e mutations, a 1 bp deletion, a 1 bp insertion, a mutation that involves bo
th a substitution and a deletion (2511AG-->C), a complex mutation in exon 6
consisting of a simultaneous 7 bp inversion and a 4 bp deletion, and the l
ast one is a G-C transversion that may be a missense mutation. Most of thes
e mutations are expected to lead to the formation of shorter truncated prot
eins lacking the carboxyl terminus of PKD2. We have also characterized a fr
equent polymorphism, Arg-Pro, at codon 28 in this gene. The clinical featur
es of these PKD2 patients are similar to the previously described, with the
mean age of end-stage renal disease being 75.5 years (SE +/- 3.8 years).
Conclusions. Our results confirm that many different mutations are likely t
o be responsible for the disease and that most pathogenic defects probably
are point or small changes in the coding region of the gene.