Localization of a gene for familial juvenile hyperuricemic nephropathy causing underexcretion-type gout to 16p12 by genome-wide linkage analysis of alarge family

Objective. Familial juvenile hyperuricemic nephropathy (FJHN, MIM 162000) i s an autosomal-dominant disease characterized by underexcretion-type hyperu ricemia, gout, and chronic renal failure. No loci responsible for this dise ase or any underexcretion-type hyperuricemia/gout have ever been identified . The aim of the study was to localize a gene responsible for FJHN by linka ge analysis, Methods. A single large family with at least 20 affected members was analyz ed. DNA was obtained from 13 affected and 18 non-affected members after lym phoblastoid cell lines were established. Initially, polymorphic data were o btained for 343 microsatellite loci covering all chromosomes except the X c hromosome, Parametric linkage analysis was performed using the obtained dat a with LINKAGE package software. Results. Following a genome-wide search using a set of highly polymorphic m icrosatellite markers, initial evidence for linkage was obtained for a mark er on chromosome 16p, We subsequently genotyped the same subjects for 12 ad ditional markers spanning similar to 30 cM on the short arm of chromosome 1 6, We obtained a maximum 2-point logarithm of odds (LOD) score of 6.04 at t heta = 0 with the marker D16S401; multipoint linkage analysis yielded a max imum LOD score of 6.14 with markers D16S401 and D16S3113, and established a minimum candidate interval of similar to 9 cM. Conclusion. A gene for FJHN was localized to a candidate interval of simila r to 9 cM at 16p12. These findings will be useful for the presymptomatic di agnosis of FJHN in some families and for testing genetic heterogeneity of F JHN in general.