Detection of translation terminating mutations in the PKD1 gene.

Since the identification of the PKD1 gene in 1994, few mutations have been found. This is mainly due to the very strong homology between a large part of the PKD1 gene and another locus on the short arm of chromosome 16. It is expected that the majority of mutations at the PKD1 locus will be small deletions, insertions and point mutations. Amplification of a piece of DNA derived from the repeated area of the PKD1 gene will result in co-amplification of DNA fragments from the other locus. Detection of mutations is significantly hampered this way. We present a procedure, using the protein truncation test, which reduces the complexity caused by the homologous sequences. We have studied a group of 20 patients with ADPKD at the 3' end of the PKD1 transcript and have produced promising results.