Familial juvenile hyperuricemic nephropathy: Localization of the gene on chromosome 16p11.2 - and evidence for genetic heterogeneity

Familial juvenile hyperuricemic nephropathy (FJHN), is an autosomal dominan t renal disease characterized by juvenile onset of hypcruricemia, gouty art hritis, and progressive renal failure at an early age. Using a genomewide l inkage analysis in three Czech affected families, we have identified, on ch romosome 16p11.2, a locus for FJHN and have found evidence for genetic hete rogeneity 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 D16S30SG; multipoint linkage anal ysis yielded a maximum HLOD score of 4.76 at the same location. Haplotype a nalysis defined a 10-cM candidate region between flanking markers D16S501 a nd D16S3113, exhibiting crossover events with the disease locus. The candid ate interval contains several genes expressed in the kidney, two of which-u romodulin and NADP-regulated thyroid-hormone-binding protein-represent prom ising candidates for further analysis.