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


CONCLUSIONS
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.
Vouk
Katja
K
Medical Centre for Molecular Biology, Institute of Biochemistry, Faculty of Medicine, Vrazov trg 2, 1000 Ljubljana, Slovenia. katjavouk@yahoo.co.uk
Strmecki
Lana
L
Stekrova
Jitka
J
Reiterova
Jana
J
Bidovec
Matjaz
M
Hudler
Petra
P
Kenig
Anton
A
Jereb
Simona
S
Zupanic-Pajnic
Irena
I
Balazic
Joze
J
Haarpaintner
Guido
G
Leskovar
Bostjan
B
Adamlje
Anton
A
Skoflic
Antun
A
Dovc
Reina
R
Hojs
Radovan
R
Komel
Radovan
R
D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008126:Lod Score; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016891:Polycystic Kidney, Autosomal Dominant / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D017524:Slovenia; D050396:TRPP Cation Channels
D008565:Membrane Proteins; D011506:Proteins; D050396:TRPP Cation Channels