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Mutation detection in the duplicated region of the polycystic kidney disease 1 ( PKD1 ) gene in PKD1‐linked Australian families
Author(s) -
McCluskey Marie,
Schiavello Tina,
Hunter Michael,
Hantke Janina,
Angelicheva Dora,
Bogdanova Nadja,
Markoff Arseni,
Thomas Mark,
Dworniczak Bernd,
Horst Juergen,
Kalaydjieva Luba
Publication year - 2002
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.10045
Subject(s) - pkd1 , missense mutation , biology , genetics , polycystic kidney disease , mutation , autosomal dominant polycystic kidney disease , exon , gene , gene mutation , microbiology and biotechnology , kidney
Screening for disease‐causing mutations in the duplicated region of the PKD1 gene was performed in 17 unrelated Australian individuals with PKD1‐linked autosomal dominant polycystic kidney disease. Exons 2–21 and 23–34 were assayed using PKD1‐specific PCR amplification and direct sequencing. We have identified 12 novel probably pathogenic DNA variants, including five truncating mutations (Q563X, c.5105delAT, c.5159delG, S2269X, c.9847delC), two in‐frame deletions (c.7472del3, c.9292del39), and two splice‐site mutations (IVS14+1G>C, IVS16+1G>T). Three of the mutations (G381C, Y2185D, G2785D) were predicted to lead to the replacement of conserved amino acid residues, with ensuing changes in protein conformation. Defects in the duplicated region of PKD1 thus account for 63% of our patients. Together with the previously detected mutations (Q4041X, R4227P) in the 3′ region of the gene, the study has achieved an overall mutation detection rate of 74%. In addition, we have detected 31 variants (nine novel and 22 previously published) that did not segregate with the disease and were considered to be neutral polymorphisms. Three of the nine novel polymorphisms were missense mutations with a predicted effect on protein conformation, emphasizing the problems of interpretation in PKD1 mutation screening. Hum Mutat 19:240–250, 2002. © 2002 Wiley‐Liss, Inc.