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: Joanna M Stacey, Jeremy J O Turner, Brian Harding, M Andrew Nesbit, Peter Kotanko, Karl Lhotta, Juan G Puig, Rosa J Torres, Rajesh V Thakker
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 88 Issue 1 Pg. 464-70 (Jan 2003) ISSN: 0021-972X [Print] United States
• PMID: 12519891 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Uric Acid

Topics

• Child
• Chromosome Mapping
• Chromosome Segregation
• Chromosomes, Human, Pair 16 (genetics)
• Female
• Genetic Heterogeneity
• Genetic Linkage
• Humans
• Hyperuricemia (genetics)
• Kidney (pathology)
• Kidney Diseases (genetics, pathology)
• Kidney Failure, Chronic (genetics)
• Male
• Pedigree
• Uric Acid (urine)