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Open Access Research article

PKD1 and PKD2 mutations in Slovenian families with autosomal dominant polycystic kidney disease

Katja Vouk1, Lana Strmecki1, Jitka Stekrova7, Jana Reiterova7, Matjaz Bidovec2, Petra Hudler1, Anton Kenig2, Simona Jereb2, Irena Zupanic-Pajnic3, Joze Balazic3, Guido Haarpaintner1, Bostjan Leskovar4, Anton Adamlje4, Antun Skoflic5, Reina Dovc5, Radovan Hojs6 and Radovan Komel1*

Author Affiliations

1 Medical Centre for Molecular Biology, Institute of Biochemistry, Faculty of Medicine, Vrazov trg 2, 1000 Ljubljana, Slovenia

2 Children's Hospital Ljubljana, Clinic for Paediatric Nephrology and Radiology Unit, Vrazov trg 1, 1000 Ljubljana, Slovenia

3 Institute of Forensic Medicine, Faculty of Medicine, Korytkova 2, 1000 Ljubljana, Slovenia

4 Trbovlje General Hospital, Dialysis Department, Rudarska 7, Trbovlje, Slovenia

5 Celje General Hospital, Nephrology Department and Dialysis Centre, Oblakova 5, 3000 Celje, Slovenia

6 Maribor General Hospital, Clinical Department for Internal Medicine, Nephrology Department, 2000 Maribor, Slovenia

7 Department of Medical Genetics and Department of Nephrology,1st Faculty of Medicine, Charles University, Albertov 2, 12800 Prague 2, Czech Republic

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BMC Medical Genetics 2006, 7:6  doi:10.1186/1471-2350-7-6

Published: 23 January 2006

Abstract

Background

Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder caused by mutations in at least two different loci. Prior to performing mutation screening, if DNA samples of sufficient number of family members are available, it is worthwhile to assign the gene involved in disease progression by the genetic linkage analysis.

Methods

We collected samples from 36 Slovene ADPKD families and performed linkage analysis in 16 of them. Linkage was assessed by the use of microsatellite polymorphic markers, four in the case of PKD1 (KG8, AC2.5, CW3 and CW2) and five for PKD2 (D4S1534, D4S2929, D4S1542, D4S1563 and D4S423). Partial PKD1 mutation screening was undertaken by analysing exons 23 and 31–46 and PKD2 .

Results

Lod scores indicated linkage to PKD1 in six families and to PKD2 in two families. One family was linked to none and in seven families linkage to both genes was possible. Partial PKD1 mutation screening was performed in 33 patients (including 20 patients from the families where linkage analysis could not be performed). We analysed PKD2 in 2 patients where lod scores indicated linkage to PKD2 and in 7 families where linkage to both genes was possible. We detected six mutations and eight polymorphisms in PKD1 and one mutation and three polymorphisms in PKD2.

Conclusion

In our study group of ADPKD patients we detected seven mutations: three frameshift, one missense, two nonsense and one putative splicing mutation. Three have been described previously and 4 are novel. Three newly described framesfift mutations in PKD1 seem to be associated with more severe clinical course of ADPKD. Previously described nonsense mutation in PKD2 seems to be associated with cysts in liver and milder clinical course.