Molecular diagnostics in autosomal dominant polycystic kidney disease: utility and limitations.
OBJECTIVE
Gene-based mutation screening is now available and has the potential to provide diagnostic confirmation or exclusion of autosomal dominant polycystic kidney disease. This study illustrates its utility and limitations in the clinical setting.


METHODS
Using a molecular diagnostic service, genomic DNA of one affected individual from each study family was screened for pathologic PKD1 and PKD2 mutations. Bidirectional sequencing was performed to identify sequence variants in all exons and splice junctions of both genes and to confirm the specific mutations in other family members. In two multiplex families, microsatellite markers were genotyped at both PDK1 and PKD2 loci, and pair-wise and multipoint linkage analysis was performed.


RESULTS
Three of five probands studied were referred for assessment of renal cystic disease without a family history of autosomal dominant polycystic kidney disease, and two others were younger at-risk members of families with autosomal dominant polycystic kidney disease being evaluated as living-related kidney donors. Gene-based mutation screening identified pathogenic mutations that provided confirmation or exclusion of disease in three probands, but in the other two, only unclassified variants were identified. In one proband in which mutation screening was indeterminate, DNA linkage studies provided strong evidence for disease exclusion.


CONCLUSIONS
Gene-based mutation screening or DNA linkage analysis should be considered in individuals in whom the diagnosis of autosomal dominant polycystic kidney disease is uncertain because of a lack of family history or equivocal imaging results and in younger at-risk individuals who are being evaluated as living-related kidney donors.
Zhao
Xiao
X
Division of Nephrology, University Health Network, Toronto, Ontario, Canada.
Paterson
Andrew D
AD
Zahirieh
Alireza
A
He
Ning
N
Wang
Kairong
K
Pei
York
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis / Q000379:methods / Q000592:standards; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D005820:Genetic Testing / Q000379:methods* / Q000592:standards*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016891:Polycystic Kidney, Autosomal Dominant / Q000175:diagnosis* / Q000235:genetics*; D050396:TRPP Cation Channels
D050396:TRPP Cation Channels