title: Genetic mapping studies of familial juvenile hyperuricemic nephropathy on chromosome 16p11-p13.
abstract: Familial juvenile hyperuricemic nephropathy (FJHN), which is inherited as an autosomal dominant disorder, is characterized by hyperuricemia, a low fractional renal excretion of urate, and chronic renal failure that is associated with interstitial fibrosis. Studies in 4 families (3 European and 1 Japanese) have mapped the gene causing autosomal dominant FJHN to chromosome 16p11-p13. To refine this location we have pursued linkage studies in 7 European families with autosomal dominant FJHN and used 11 chromosome 16p11-p13 polymorphic loci whose order has been established as 16pter-D16S3069-D16S3060-D16S3041-D16S3036-D16S3046-[D16S403,D16S417]-D16S420-D16S3113-D16S401-D16S3133-16cen. Cosegregation between these polymorphic loci and FJHN was observed in 5 of the families, and linkage was established between FJHN and 6 loci (peak LOD score, 5.32 with D16S417, at 0% recombination), with the most likely location of FJHN being within a 22-centimorgan interval flanked centromerically by D16S401 and telomerically by D16S3069. Furthermore, FJHN in 2 families was found not to be linked to chromosome 16p11-p13, thereby demonstrating genetic heterogeneity. Thus, 5 additional families with FJHN showing linkage to chromosome 16p11-p13 loci have been identified, and genetic heterogeneity has been demonstrated in more than 25% of FJHN families. These results will facilitate the characterization of this gene regulating urate metabolism.
authors.affiliation: Molecular Endocrinology Group, Nuffield Department of Medicine, Botnar Research Center, University of Oxford, Oxford, United Kingdom OX3 7LD.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Stacey
authors.forename: Jeremy J O
authors.initials: JJ
authors.lastname: Turner
authors.forename: Brian
authors.initials: B
authors.lastname: Harding
authors.forename: M Andrew
authors.initials: MA
authors.lastname: Nesbit
authors.forename: Peter
authors.initials: P
authors.lastname: Kotanko
authors.forename: Karl
authors.initials: K
authors.lastname: Lhotta
authors.forename: Juan G
authors.initials: JG
authors.lastname: Puig
authors.forename: Rosa J
authors.initials: RJ
authors.lastname: Torres
authors.forename: Rajesh V
authors.initials: RV
authors.lastname: Thakker
mesh_terms: D002648:Child; D002874:Chromosome Mapping; D020090:Chromosome Segregation; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006801:Humans; D033461:Hyperuricemia / Q000235:genetics*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000235:genetics; D008297:Male; D010375:Pedigree; D014527:Uric Acid / Q000652:urine
chemical_list: D014527:Uric Acid