Mapping of gene loci for nephronophthisis type 4 and Senior-Loken syndrome, to chromosome 1p36.

ABSTRACT: 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 (Z(max)) of 8.9 (at D1S253). We thus identified a new locus, NPHP4

SUBMITTER: Schuermann MJ 

PROVIDER: S-EPMC447598 | biostudies-literature | 2002 May

REPOSITORIES: biostudies-literature