Author/Editor		Vouk, Katja; Strmecki, Lana; Bidovec, Matjaž; Hudler, Petra; Jereb, Simona; Zupanič-Pajnič, Irena; Balažic, Jože; Leskovar, Boštjan; Hojs, Radovan; Komel, Radovan
Title		PKD1 and PKD2 mutations in Slovenian families with autosomal dominant polycystic kidney disease
Type		članek
Source		BMC Med Genet
Vol. and No.		Letnik 7, št. 6
Publication year		2006
Volume		str. 1-26
Language		eng
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 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 two patients where Lod scores indicated linkage to PKD2 and in seven 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 four are novel. Three newly described frameshift mutations in PKD1 seem to be associated with a more severe clinical course of the disease. Previously described nonsense mutation in PKD2 seems to be associated with cysts in the liver and a milder clinical course.
Descriptors		KIDNEY, POLYCYSTIC, AUTOSOMAL DOMINANT MUTATION LINKAGE (GENETICS) MICROSATELLITE REPEATS EXONS POLYMERASE CHAIN REACTION PEDIGREE