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Presymptomatic molecular diagnosis of autosomal dominant polycystic kidney disease using PKD1‐and PKD2‐linked markers in Cypriot families
Author(s) -
Deltas C. Constantinou,
Christodoulou Kyproula,
Tjakouri Chrysa,
Pierides Alkis
Publication year - 1996
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.1996.tb02339.x
Subject(s) - pkd1 , proband , autosomal dominant polycystic kidney disease , locus (genetics) , genetics , polycystic kidney disease , haplotype , genetic linkage , biology , genetic marker , locus heterogeneity , genetic heterogeneity , medicine , phenotype , kidney , gene , genotype , mutation
Autosomal dominant polycystic kidney disease (ADPKD), is a heterogeneous disorder, primarily characterized by the formation of cysts in the kidneys, and the late development in life of progressive chronic kidney failure. Three genes are implicated in causing ADPKD. One on chromosome 16, PKD1, accounts for 85–90% of all cases, and the PKD2 gene on chromosome 4 accounts for the remainder. A very rare third locus is still of unknown location. We used PKD1‐and PKD2‐linked polymorphic markers to make the diagnosis of ADPKD in young presymptomatic members in affected families. We showed that in young members of families where clinical diagnosis cannot be definitively established, molecular linkage 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 disease with a PKD1‐linked haplotype which originated in a non‐affected 78‐year‐old father. Analysis with PKD2‐linked markers excluded this locus. 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 affected person, most probably because of a novel mutation in one of her father's chromosomes. In conclusion, the combined use of markers around the PKD1 and the PKD2 locus provides more definitive answers in cases where presymptomatic diagnosis is requested by concerned families.