HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: CJN.03430807v1 3/1/146    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhao, X. Articles by Pei, Y. Search for Related Content PubMed PubMed Citation Articles by Zhao, X. Articles by Pei, Y. Related Collections Related Article

Molecular Diagnostics in Autosomal Dominant Polycystic Kidney Disease: Utility and Limitations

Xiao Zhao^*, Andrew D. Paterson, Alireza Zahirieh^*, Ning He^*, Kairong Wang^*, and York Pei^*

^* Division of Nephrology, University Health Network and University of Toronto, and Program in Genetics and Genomic Biology, Hospital for Sick Children and Department of Public Health Sciences, University of Toronto, Toronto, Ontario, Canada

Correspondence: Dr. York Pei, Division of Nephrology, University Health Network, 8N838, 585 University Avenue, Toronto, Ontario, Canada M5G 2N2. Phone: 416-340-4257; Fax: 416-340-4999; E-mail: york.pei{at}uhn.on.ca

Background and objectives: 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.

Design, setting, participants, & measurements: 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.

Related Article

Molecular Diagnostics of ADPKD Coming of Age

Peter C. Harris and Sandro Rossetti
Clin. J. Am. Soc. Nephrol. 2008 3: 1-2. [Full Text] [PDF]

This article has been cited by other articles:

				M. Barua, O. Cil, A. D. Paterson, K. Wang, N. He, E. Dicks, P. Parfrey, and Y. Pei Family History of Renal Disease Severity Predicts the Mutated Gene in ADPKD J. Am. Soc. Nephrol., August 1, 2009; 20(8): 1833 - 1838. [Abstract] [Full Text] [PDF]

				J. J. Grantham Autosomal Dominant Polycystic Kidney Disease N. Engl. J. Med., October 2, 2008; 359(14): 1477 - 1485. [Full Text] [PDF]