Evidence of a third ADPKD locus is not supported by re-analysis of designated PKD3 families. Kidney Int 2014 Feb;85(2):383-92
Date
06/14/2013Pubmed ID
23760289Pubmed Central ID
PMC3883953DOI
10.1038/ki.2013.227Scopus ID
2-s2.0-84893266233 (requires institutional sign-in at Scopus site) 31 CitationsAbstract
Mutations to PKD1 and PKD2 are associated with autosomal dominant polycystic kidney disease (ADPKD). The absence of apparent PKD1/PKD2 linkage in five published European or North American families with ADPKD suggested a third locus, designated PKD3. Here we re-evaluated these families by updating clinical information, re-sampling where possible, and mutation screening for PKD1/PKD2. In the French-Canadian family, we identified PKD1: p.D3782_V3783insD, with misdiagnoses in two individuals and sample contamination explaining the lack of linkage. In the Portuguese family, PKD1: p.G3818A segregated with the disease in 10 individuals in three generations with likely misdiagnosis in one individual, sample contamination, and use of distant microsatellite markers explaining the linkage discrepancy. The mutation PKD2: c.213delC was found in the Bulgarian family, with linkage failure attributed to false positive diagnoses in two individuals. An affected son, but not the mother, in the Italian family had the nonsense mutation PKD1: p.R4228X, which appeared de novo in the son, with simple cysts probably explaining the mother's phenotype. No likely mutation was found in the Spanish family, but the phenotype was atypical with kidney atrophy in one case. Thus, re-analysis does not support the existence of a PKD3 in ADPKD. False positive diagnoses by ultrasound in all resolved families shows the value of mutation screening, but not linkage, to understand families with discrepant data.
Author List
Paul BM, Consugar MB, Ryan Lee M, Sundsbak JL, Heyer CM, Rossetti S, Kubly VJ, Hopp K, Torres VE, Coto E, Clementi M, Bogdanova N, de Almeida E, Bichet DG, Harris PCAuthor
Ryan M. Lee MD Instructor in the Neurology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Canada
Child
DNA Mutational Analysis
Diagnostic Errors
Europe
False Positive Reactions
Female
Genetic Linkage
Genetic Loci
Genetic Predisposition to Disease
Genetic Testing
Haplotypes
Heredity
Humans
Male
Middle Aged
Mutation
Pedigree
Phenotype
Polycystic Kidney, Autosomal Dominant
Predictive Value of Tests
TRPP Cation Channels
Ultrasonography
Young Adult
