Identification of a gene locus for Senior-Løken syndrome in the region of the nephronophthisis type 3 gene

Abstract

Senior-Løken syndrome is an autosomal recessive disease with the main features of nephronophthisis (NPH) and Leber congenital amaurosis. The gene for adolescent nephronophthisis (NPHP3) was recently localized to chromosome 3q21-q22. The hypothesis was tested that Senior-Løken syndrome (SLS) might localize to the same region by studying a kindred of German ancestry with extended consanguinity and typical findings of SLS. Twenty highly polymorphic markers located in the vicinity of the NPHP3 genetic region were tested. Haplotype analysis revealed homozygosity by descent in affected individuals, and linkage analysis yielded a parametric maximum multipoint logarithm of likelihood of odds (LOD) score of 3.14, thus identifying the first locus for SLS. The SLS1 locus is flanked by D3S1587 and D3S621 and contains a 14-cM interval that contains the whole critical NPHP3 region. Three additional families with SLS were studied, and evidence for genetic heterogeneity in one of them was found. Localization of a SLS locus to the region of NPHP3 opens the possibilities of both diseases arising by mutations within the same pleiotropic gene or two adjacent genes.