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. and 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: 51-58. doi:10.1007/s00439-010-0897-1


Author 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.
Title Genome-wide study of familial juvenile hyperuricaemic (gouty) nephropathy (FJHN) indicates a new locus, FJHN3, linked to chromosome 2p22.1-p21
Journal name Human Genetics   Check publisher's open access policy
ISSN 0340-6717
1432-1203
Publication date 2011-01
Year available 2010
Sub-type Article (original research)
DOI 10.1007/s00439-010-0897-1
Volume 129
Issue 1
Start page 51
End page 58
Total pages 8
Editor D. N. Cooper
Th. J. Hudson
Place of publication Heidelberg, Germany
Publisher Springer
Collection year 2011
Language eng
Formatted abstract
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-) on chromosomes 16p12, 1q32.1, and 17q12, respectively. However, UMOD, REN or HNF- 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- 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.
© Springer-Verlag 2010
Keyword Hepatocyte nuclear factor-1-beta
Cystic kidney-disease
Tamm-Horsfall protein
Autosomal-dominant
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 26 October 2010

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
UQ Diamantina Institute Publications
 
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Created: Fri, 25 Feb 2011, 10:42:51 EST by Kylie Hengst on behalf of UQ Diamantina Institute