Novel PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease (ADPKD).
BACKGROUND
Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic renal disorder with an incidence of 1:1000. Mutations in two genes (PKD1 and PKD2) have been identified as causative. Eighty-five percent of patients with ADPKD carry their mutation in the PKD1 gene. So far, > 500 mutations for PKD1 and > 120 mutations for PKD2, respectively, are known.


METHODS
In this study, we performed mutation analysis of PKD1 and PKD2 by exon sequencing in patients during routine molecular diagnostics for ADPKD.


RESULTS
In total, 60 mutations were identified in 93 patients representing a mutation detection efficiency of 64.5%. Fifty-two mutations were identified in PKD1 (86.7%) and 8 in PKD2 (13.3%). These include 41 novel mutations detected in PKD1 and 5 novel mutations in PKD2. Accordingly, our data expand the spectrum of known PKD mutations by 8% for PKD1 (41/513) and 4.2% for PKD2 (5/120). These results are in agreement with the detection ranges of 42%, 63% and 64% for definitive disease-causing mutations, and 78%, 86% and 89% for all identified variants reported in several comprehensive mutation screening reports.


CONCLUSIONS
The increased number of known mutations will facilitate future studies into genotype-phenotype correlations.
Center for Human Genetics and Laboratory Medicine Dr Klein and Dr Rost, Martinsried, Germany. julia.hoefele@medizinische-genetik.de
Julia
J
Hoefele
Karin
K
Mayer
Manuela
M
Scholz
Hanns-Georg
HG
Klein
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002648:Child; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000151:congenital / Q000235:genetics*; D011379:Prognosis; D050396:TRPP Cation Channels / Q000235:genetics*; D055815:Young Adult
D050396:TRPP Cation Channels