Genome-wide study of familial juvenile hyperuricaemic (gouty) nephropathy (FJHN) indicates a new locus, FJHN3, linked to chromosome 2p22.1-p21

Piret, Sian E., Danoy, Patrick, Dahan, Karin, Reed, Anita A. C., Pryce, Karena, Wong, William, Torres, Rosa J., Puig, Juan G., Müller, Thomas, Kotanko, Peter, Lhotta, Karl, Devuyst, Olivier, Brown, Matthew A., & Thakker, Rajesh V. (2011) Genome-wide study of familial juvenile hyperuricaemic (gouty) nephropathy (FJHN) indicates a new locus, FJHN3, linked to chromosome 2p22.1-p21. Human Genetics, 129(1), pp. 51-58.

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Familial juvenile hyperuricaemic (gouty) nephropathy (FJHN), is an autosomal dominant disease associated with a reduced fractional excretion of urate, and progressive renal failure. FJHN is genetically heterogeneous and due to mutations of three genes: uromodulin (UMOD), renin (REN) and hepatocyte nuclear factor-1beta (HNF-1β) on chromosomes 16p12, 1q32.1, and 17q12, respectively. However, UMOD, REN or HNF-1β mutations are found in only ~45% of FJHN probands, indicating the involvement of other genetic loci in ~55% of probands. To identify other FJHN loci, we performed a single nucleotide polymorphism (SNP)-based genome-wide linkage analysis, in six FJHN families in whom UMOD, HNF-1β and REN mutations had been excluded. Parametric linkage analysis using a 'rare dominant' model established linkage in five of the six FJHN families, with a LOD score >+3, at 0% recombination, between FJHN and SNPs at chromosome 2p22.1-p21. Analysis of individual recombinants in two unrelated affected individuals defined a ~5.5 Mbp interval, flanked telomerically by SNP RS372139 and centromerically by RS896986 that contained the locus, designated FJHN3. The interval contains 28 genes, and DNA sequence analysis of the most likely candidate, solute carrier family 8 member 1 (SLC8A1), did not identify any abnormalities in the FJHN3 probands. FJHN3 is likely located within a ~5.5 Mbp interval on chromosome 2p22.1-p21, and identifying the genetic abnormality will help to further elucidate mechanisms predisposing to gout and renal failure.

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ID Code: 89361
Item Type: Journal Article
Refereed: Yes
Keywords: hepatocyte nuclear factor 1beta, protein subunit, renin, solute carrier family 8 member 1, Tamm Horsfall glycoprotein, unclassified drug, adolescent, adult, article, chromosome 16p, chromosome 1q, chromosome 2p, clinical article, disease predisposition, DNA determination, DNA sequence, familial disease, familial juvenile hyperuricaemic nephropathy, family, female, gene locus, gene mutation, genetic linkage, genome, gout, human, kidney failure, male, priority journal, scoring system, single nucleotide polymorphism, telomere, uric acid nephropathy, Chromosomes, Human, Pair 2, Genetic Heterogeneity, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Hyperuricemia, Kidney Diseases, Kidney Failure, Chronic, Pedigree, Uric Acid
DOI: 10.1007/s00439-010-0897-1
ISSN: 0340-6717
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 21 Oct 2015 03:57
Last Modified: 26 Feb 2016 03:23

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