title: Localization of a gene for familial juvenile hyperuricemic nephropathy causing underexcretion-type gout to 16p12 by genome-wide linkage analysis of a large family.
abstract: OBJECTIVE
  Familial juvenile hyperuricemic nephropathy (FJHN, MIM 162000) is an autosomal-dominant disease characterized by underexcretion-type hyperuricemia, gout, and chronic renal failure. No loci responsible for this disease or any underexcretion-type hyperuricemia/gout have ever been identified. The aim of the study was to localize a gene responsible for FJHN by linkage analysis.
  
  
  METHODS
  A single large family with at least 20 affected members was analyzed. DNA was obtained from 13 affected and 18 non-affected members after lymphoblastoid cell lines were established. Initially, polymorphic data were obtained for 343 microsatellite loci covering all chromosomes except the X chromosome. Parametric linkage analysis was performed using the obtained data with LINKAGE package software.
  
  
  RESULTS
  Following a genome-wide search using a set of highly polymorphic microsatellite markers, initial evidence for linkage was obtained for a marker on chromosome 16p. We subsequently genotyped the same subjects for 12 additional markers spanning approximately 30 cM on the short arm of chromosome 16. We obtained a maximum 2-point logarithm of odds (LOD) score of 6.04 at theta = 0 with the marker D16S401; multipoint linkage analysis yielded a maximum LOD score of 6.14 with markers D16S401 and D16S3113, and established a minimum candidate interval of approximately 9 cM.
  
  
  CONCLUSIONS
  A gene for FJHN was localized to a candidate interval of approximately 9 cM at 16p12. These findings will be useful for the presymptomatic diagnosis of FJHN in some families and for testing genetic heterogeneity of FJHN in general.
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kamatani
authors.forename: M
authors.initials: M
authors.lastname: Moritani
authors.forename: H
authors.initials: H
authors.lastname: Yamanaka
authors.forename: F
authors.initials: F
authors.lastname: Takeuchi
authors.forename: T
authors.initials: T
authors.lastname: Hosoya
authors.forename: M
authors.initials: M
authors.lastname: Itakura
mesh_terms: D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006073:Gout / Q000209:etiology* / Q000235:genetics; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000235:genetics; D008126:Lod Score; D008297:Male; D010375:Pedigree; D014527:Uric Acid / Q000097:blood*
chemical_list: D014527:Uric Acid