DO: 0060062;
Cytogenetic location: 2p22.1-p21 Genomic coordinates (GRCh38) : 2:38,300,001-47,500,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 2p22.1-p21 | Hyperuricemic nephropathy, familial juvenile, 3 | 614227 | Autosomal dominant | 2 |
Familial juvenile hyperuricemia nephropathy-3 may be a distinct form of autosomal dominant tubulointerstitial kidney disease (ADTKD); however, because the mapping of the disorder in the families described by Piret et al. (2011) is tentative, it is possible that the families have a form of the disorder described in the ADTKD series (see ADTKD1, 162000).
Piret et al. (2011) performed SNP-based genomewide linkage analysis in 6 multiplex families with familial juvenile hyperuricemic nephropathy, including 3 previously studied by Williams et al. (2009) and 2 previously studied by Stacey et al. (2003), in which mutations in UMOD (191845), REN (179820), and HNF1B (189907) had been excluded. Parametric linkage analysis using a 'rare dominant' model established linkage in 5 of the 6 HNFJ families, with a lod score greater than 3 (theta = 0) at chromosome 2p22.1-p21. Recombination events in 2 unrelated affected individuals defined an approximately 5.5-Mb disease interval, flanked by rs372139 and rs896986, a locus that the authors designated FJHN3.
Exclusion Studies
Piret et al. (2011) analyzed function and expression patterns of 28 genes contained in the candidate interval on chromosome 2p22.1-p21. Sequence analysis of the most likely candidate, SLC8A1 (182305), in probands from 5 families with renal disease mapping to that region did not reveal any mutations.
Piret, S. E., Danoy, P., Dahan, K., Reed, A. A. C., Pryce, K., Wong, W., Torres, R. J., Puig, J. G., Muller, T., Kotanko, P., Lhotta, K., Devuyst, O., Brown, M. A., Thakker, R. V. Genome-wide study of familial juvenile hyperuricaemic (gouty) nephropathy (FJHN) indicates a new locus, FJHN3, linked to chromosome 2p22.1-p21. Hum. Genet. 129: 51-58, 2011. [PubMed: 20976470] [Full Text: https://doi.org/10.1007/s00439-010-0897-1]
Stacey, J. M., Turner, J. J. O., Harding, B., Nesbit, M. A., Kotanko, P., Lhotta, K., Puig, J. G., Torres, R. J., Thakker, R. V. Genetic mapping studies of familial juvenile hyperuricemic nephropathy on chromosome 16p11-p13. J. Clin. Endocr. Metab. 88: 464-470, 2003. [PubMed: 12519891] [Full Text: https://doi.org/10.1210/jc.2002-021268]
Williams, S. E., Reed, A. A. C., Galvanovskis, J., Antignac, C., Goodship, T., Karet, F. E., Kotanko, P., Lhotta, K., Moriniere, V., Williams, P., Wong, W., Rorsman, P., Thakker, R. V. Uromodulin mutations causing familial juvenile hyperuricaemic nephropathy lead to protein maturation defects and retention in the endoplasmic reticulum. Hum. Molec. Genet. 18: 2963-2974, 2009. [PubMed: 19465746] [Full Text: https://doi.org/10.1093/hmg/ddp235]