PKD1 and PKD2 mutations in Slovenian families with autosomal dominant polycystic kidney disease
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
BMC Medical Genetics 2006, 7:6 doi:10.1186/1471-2350-7-6Published: 23 January 2006
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.
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 .
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.
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.