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

• Huvudupphovsmän: Adamlje Anton (Författare, medförfattare), Leskovar Bostjan (Författare, medförfattare), Haarpaintner Guido (Författare, medförfattare), Balazic Joze (Författare, medförfattare), Zupanic-Pajnic Irena (Författare, medförfattare), Jereb Simona (Författare, medförfattare), Kenig Anton (Författare, medförfattare), Hudler Petra (Författare, medförfattare), Bidovec Matjaz (Författare, medförfattare), Reiterova Jana (Författare, medförfattare), Stekrova Jitka (Författare, medförfattare), Strmecki Lana (Författare, medförfattare), Vouk Katja (Författare, medförfattare), Skoflic Antun (Författare, medförfattare), Dovc Reina (Författare, medförfattare), Hojs Radovan (Författare, medförfattare), Komel Radovan (Författare, medförfattare)
• Materialtyp: Bok
• Publicerad: BMC, 2006-01-01T00:00:00Z.
• Ämnen: article
• Länkar: Connect to this object online.

Sammanfattning

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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 <it>PKD1 </it>(KG8, AC2.5, CW3 and CW2) and five for <it>PKD2 </it>(D4S1534, D4S2929, D4S1542, D4S1563 and D4S423). Partial <it>PKD1 </it>mutation screening was undertaken by analysing exons 23 and 31-46 and <it>PKD2 </it>.</p> <p>Results</p> <p>Lod scores indicated linkage to <it>PKD1 </it>in six families and to <it>PKD2 </it>in two families. One family was linked to none and in seven families linkage to both genes was possible. Partial <it>PKD1 </it>mutation screening was performed in 33 patients (including 20 patients from the families where linkage analysis could not be performed). We analysed <it>PKD2 </it>in 2 patients where lod scores indicated linkage to <it>PKD2 </it>and in 7 families where linkage to both genes was possible. We detected six mutations and eight polymorphisms in <it>PKD1 </it>and one mutation and three polymorphisms in <it>PKD2</it>.</p> <p>Conclusion</p> <p>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 <it>PKD1 </it>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.</p>

Beskrivning

10.1186/1471-2350-7-6
1471-2350