Localization of a gene for familial juvenile hyperuricemic nephropathy causing underexcretion-type gout to 16p12 by genome-wide linkage analysis of a large family.
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.
Kamatani
N
N
Institute of Rheumatology, Tokyo Women's Medical University, Japan.
Moritani
M
M
Yamanaka
H
H
Takeuchi
F
F
Hosoya
T
T
Itakura
M
M
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*
D014527:Uric Acid