This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stacey, J. M. Articles by Thakker, R. V. Search for Related Content PubMed PubMed Citation Articles by Stacey, J. M. Articles by Thakker, R. V.

Genetic Mapping Studies of Familial Juvenile Hyperuricemic Nephropathy on Chromosome 16p11-p13

Molecular Endocrinology Group, Nuffield Department of Medicine, Botnar Research Center, University of Oxford (J.M.S., J.J.O.T., B.H., M.A.N., R.V.T.), Oxford, United Kingdom OX3 7LD; Department of Internal Medicine, Krankenhaus der Barmherzigen Brueder (Teaching Hospital KFU, Graz) (P.K.), Graz, Austria A-8020; Department of Clinical Nephrology, Innsbruck University Hospital (K.L.), Innsbruck, Austria A-6020; and Servicio de Medicina Interna, Hospital General (J.G.P., R.J.T.), 28046 Madrid, Spain

Address all correspondence and requests for reprints to: Prof. R. V. Thakker, Molecular Endocrinology Group, Nuffield Department of Medicine, Botnar Research Center, University of Oxford, Nuffield Orthopedic Center, Headington, Oxford, United Kingdom OX3 7LD. E-mail: rajesh.thakker{at}ndm.ox.ac.uk.

Familial juvenile hyperuricemic nephropathy (FJHN), which is inherited as an autosomal dominant disorder, is characterized by hyperuricemia, a low fractional renal excretion of urate, and chronic renal failure that is associated with interstitial fibrosis. Studies in 4 families (3 European and 1 Japanese) have mapped the gene causing autosomal dominant FJHN to chromosome 16p11-p13. To refine this location we have pursued linkage studies in 7 European families with autosomal dominant FJHN and used 11 chromosome 16p11-p13 polymorphic loci whose order has been established as 16pter-D16S3069-D16S3060-D16S3041-D16S3036-D16S3046-[D16S403,D16S417]-D16S420-D16S3113-D16S401-D16S3133-16cen. Cosegregation between these polymorphic loci and FJHN was observed in 5 of the families, and linkage was established between FJHN and 6 loci (peak LOD score, 5.32 with D16S417, at 0% recombination), with the most likely location of FJHN being within a 22-centimorgan interval flanked centromerically by D16S401 and telomerically by D16S3069. Furthermore, FJHN in 2 families was found not to be linked to chromosome 16p11-p13, thereby demonstrating genetic heterogeneity. Thus, 5 additional families with FJHN showing linkage to chromosome 16p11-p13 loci have been identified, and genetic heterogeneity has been demonstrated in more than 25% of FJHN families. These results will facilitate the characterization of this gene regulating urate metabolism.

This work was supported by the United Kingdom Medical Research Council (to J.M.S., J.J.O.T., B.H., M.A.N., and R.V.T.).

J.M.S. and J.J.O.T. contributed equally to this work.

J.J.O.T. is a Medical Research Council training fellow.

Abbreviations: FJHN, Familial juvenile hyperuricemic nephropathy; MCKD1, medullary cystic kidney disease type 1.

This article has been cited by other articles:

				S. E. Williams, A. A.C. Reed, J. Galvanovskis, C. Antignac, T. Goodship, F. E. Karet, P. Kotanko, K. Lhotta, V. Moriniere, P. Williams, et al. Uromodulin mutations causing familial juvenile hyperuricaemic nephropathy lead to protein maturation defects and retention in the endoplasmic reticulum Hum. Mol. Genet., August 15, 2009; 18(16): 2963 - 2974. [Abstract] [Full Text] [PDF]

				L. Rampoldi, G. Caridi, D. Santon, F. Boaretto, I. Bernascone, G. Lamorte, R. Tardanico, M. Dagnino, G. Colussi, F. Scolari, et al. Allelism of MCKD, FJHN and GCKD caused by impairment of uromodulin export dynamics Hum. Mol. Genet., December 15, 2003; 12(24): 3369 - 3384. [Abstract] [Full Text] [PDF]