PRESYMPTOMATIC MOLECULAR DIAGNOSIS OF AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE USING PKD1-LINKED AND PKD2-LINKED MARKERS IN CYPRIOT FAMILIES

Autosomal dominant polycystic kidney disease (ADPKD), is a heterogeneo us disorder, primarily characterized by the formation of cysts in the kidneys, and the late development in life of progressive chronic kidne y failure. Three genes are implicated in causing ADPKD. One on chromos ome 16, PKD1, accounts for 85-90% of all cases, and the PKD2 gene on c hromosome 4 accounts for the remainder. A very rare third locus is sti ll of unknown location. We used PKD1- and PKD2-linked polymorphic mark ers to make the diagnosis of ADPKD in young presymptomatic members in affected families. We showed that in young members of families where c linical diagnosis cannot be definitively established, molecular linkag e analysis can assist clinicians in the diagnosis. In one family a 24- year old had one cyst on the right kidney; however, molecular analysis showed clearly that he had inherited the normal haplotype. In another family, in one part of the pedigree there was co-inheritance of the d isease with a PKD1-linked haplotype which originated in a non-affected 78-year-old father, Analysis with PKD2-linked markers excluded this l ocus. The data can be explained in one of two ways. Either this family phenotype is linked to a third locus, or the proband was the first af fected person, most probably because of a novel mutation in one of her father's chromosomes. In conclusion, the combined use of markers arou nd the PKD1 and the PKD2 locus provides more definitive answers in cas es where presymptomatic diagnosis is requested by concerned families.