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          Institute: MPI für molekulare Genetik     Collection: Research Group Development and Disease     Display Documents

ID: 26832.0, MPI für molekulare Genetik / Research Group Development and Disease
Mapping of Gene Loci for Nephronophthisis Type 4 and Senior-Løken Syndrome, to Chromosome 1p36
Authors:Schuermann, Maria J.; Otto, Edgar; Becker, Achim; Saar, Katrin; Rüschendorf, Franz; Polak, Bettine C.; Ala-Mello, Sirpa; Hoefele, Julia; Wiedensohler, Alexander; Haller, Maria; Omran, Heymut; Nürnberg, Peter; Hildebrandt, Friedhelm
Date of Publication (YYYY-MM-DD):2002-03-27
Title of Journal:American Journal of Human Genetics
Issue / Number:5
Start Page:1240
End Page:1246
Review Status:not specified
Audience:Experts Only
Abstract / Description:For nephronophthisis (NPHP), the primary genetic cause of chronic renal failure in young adults, three loci have been mapped. To identify a new locus for NPHP, we here report on total-genome linkage analysis in seven families with NPHP, in whom we had excluded linkage to all three known NPHP loci. LOD scores >1 were obtained at nine loci, which were then fine mapped at 1-cM intervals. Extensive total-genome haplotype analysis revealed homozygosity in one family, in the region of the PCLN1 gene. Subsequent mutational analysis in this gene revealed PCLN1 mutations, thereby allowing exclusion of this family as a phenocopy. Multipoint linkage analysis for the remaining six families with NPHP together yielded a maximum LOD score (Zmax) of 8.9 (at D1S253). We thus identified a new locus, NPHP4, for nephronophthisis. Markers D1S2660 and D1S2642 are flanking NPHP4 at a 2.9-cM critical interval. In one family with NPHP4, extensive genealogical studies were conducted, revealing consanguinity during the 17th century. On the basis of haplotype sharing by descent, we obtained a multipoint Zmax of 5.8 for D1S253 in this kindred alone. In addition, we were able to localize to the NPHP4 locus a new locus for Senior-Løken syndrome, an NPHP variant associated with retinitis pigmentosa.
External Publication Status:published
Document Type:Article
Communicated by:Stefan Mundlos
Affiliations:MPI für molekulare Genetik
External Affiliations:University Children's Hospital, Freiburg University, Freiburg
Gene Mapping Center, Max-Delbrück Center for Molecular Medicine, Berlin-Buch
Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn
Vrieje Universiteit Academisch Ziekenhuis, Department of Ophthalmology, Amsterdam
The Family Federation of Finland, Helsinki
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