MUTATION DETECTION IN THE REPEATED PART OF THE PKD1 GENE

The principle cause of one of the most prevalent genetic disorders, au tosomal dominant polycystic kidney disease, involves mutations in the PKD1 gene. However, since its identification in 1994, only 27 mutation s have been published. Detection of mutations has been complicated bec ause the greater part of the gene lies within a genomic region that is reiterated several times at another locus on chromosome 16. Amplifica tion of DNA fragments in the repeated part of the PKD1 gene will lead to coamplification of highly homologous fragments derived from this ot her locus. These additional fragments severely hamper point-mutation d etection. None of the point mutations published to date are located in the repeated part of the PKD1 gene. However, we have reduced the prob lems posed by the strong homology, by using the protein-truncation tes t, and we have identified eight novel mutations, seven of which are lo cated in the repeated part of the PKD1 gene.