title: Familial juvenile hyperuricemic nephropathy: localization of the gene on chromosome 16p11.2-and evidence for genetic heterogeneity.
abstract: 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.
authors.affiliation: Institute for Inherited Metabolic Disorders, 128 00 Prague 2, Czech Republic.
authors.forename: B
authors.initials: B
authors.lastname: Stibůrková
authors.forename: J
authors.initials: J
authors.lastname: Majewski
authors.forename: I
authors.initials: I
authors.lastname: Sebesta
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Ott
authors.forename: S
authors.initials: S
authors.lastname: Kmoch
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D003434:Crossing Over, Genetic / Q000235:genetics; D018153:Czech Republic; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D018740:Genetic Heterogeneity; D006073:Gout / Q000150:complications* / Q000235:genetics* / Q000378:metabolism / Q000652:urine; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009088:Mucoproteins / Q000235:genetics; D010375:Pedigree; D019683:Penetrance; D051437:Renal Insufficiency / Q000150:complications* / Q000235:genetics* / Q000378:metabolism / Q000652:urine; D013963:Thyroid Hormones; D014527:Uric Acid / Q000097:blood / Q000378:metabolism*; D058949:Uromodulin; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D009088:Mucoproteins; D013963:Thyroid Hormones; D014527:Uric Acid; D058949:Uromodulin; D000097810:Thyroid Hormone-Binding Proteins; C548612:UMOD protein, human