Familial juvenile hyperuricemic nephropathy (FJHN), is an autosomal dominant renal disease characterized by juvenile onset of hyperuricemia, gouty arthritis, and progressive renal failure at an early age. Using a genomewide linkage analysis in three Czech affected families, we have identified, on chromosome 16p11.2, a locus for FJHN and have found evidence for genetic heterogeneity and reduced penetrance of the disease. The maximum two-point LOD score calculated with allowance for heterogeneity (HLOD) was 4.70, obtained at recombination fraction 0, with marker D16S3036; multipoint linkage analysis yielded a maximum HLOD score of 4.76 at the same location. Haplotype analysis defined a 10-cM candidate region between flanking markers D16S501 and D16S3113, exhibiting crossover events with the disease locus. The candidate interval contains several genes expressed in the kidney, two of which-uromodulin and NADP-regulated thyroid-hormone-binding protein-represent promising candidates for further analysis.

• MeSH
• Crossing Over, Genetic genetics   MeSH
• Child MeSH
• Gout complications   genetics   metabolism   urine   MeSH
• Genes, Dominant genetics   MeSH
• Adult MeSH
• Genetic Heterogeneity * MeSH
• Haplotypes genetics   MeSH
• Thyroid Hormones * MeSH
• Uric Acid blood   metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Chromosomes, Human, Pair 16 genetics   MeSH
• Lod Score MeSH
• Chromosome Mapping MeSH
• Membrane Proteins genetics   MeSH
• Adolescent MeSH
• Mucoproteins genetics   MeSH
• Penetrance MeSH
• Renal Insufficiency complications   genetics   metabolism   urine   MeSH
• Pedigree MeSH
• Carrier Proteins genetics   MeSH
• Uromodulin MeSH
• Thyroid Hormone-Binding Proteins MeSH
• Age of Onset MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• Thyroid Hormones * MeSH
• Uric Acid MeSH
• Membrane Proteins MeSH
• Mucoproteins MeSH
• Carrier Proteins MeSH
• UMOD protein, human MeSH Browser
• Uromodulin MeSH