Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Eur J Hum Genet
2013 Oct 01;2110:1067-73. doi: 10.1038/ejhg.2013.3.
Show Gene links
Show Anatomy links
Novel allelic variants and evidence for a prevalent mutation in URAT1 causing renal hypouricemia: biochemical, genetics and functional analysis.
Stiburkova B
,
Sebesta I
,
Ichida K
,
Nakamura M
,
Hulkova H
,
Krylov V
,
Kryspinova L
,
Jahnova H
.
???displayArticle.abstract???
Renal hypouricemia (RHUC) is a heterogeneous inherited disorder characterized by impaired tubular uric acid (UA) transport with severe complications, such as acute kidney injury (AKI). Type 1 is caused by a loss-of-function mutation in the SLC22A12 gene (URAT1), type 2 in the SLC2A9 gene (GLUT9). This article describes three Czech families with RHUC type 1. The serum UA in the probands was 0.9, 1.1 and 0.5 mg/dl and expressed as an increase in the fractional excretion of UA (48, 43 and 39%). The sequencing analysis of SLC22A12 revealed three novel variants: p.G366R, p.T467M and a deletion p.L415_G417del. A detailed metabolic investigation in proband C for progressive visual failure supported suspicion of neuronal ceroid lipofuscinosis type 7 conditioned by the mutation in the MFSD8 gene. Functional studies showed significantly decreased urate uptake and a mis-localized URAT1 signal in p.G366R, p.L415_G417del and p.T467M. Furthermore, colocalization studies showed accumulation of URAT1 protein in the endoplasmic reticulum. The findings suggest that loss-of-function mutations cause RHUC via loss of UA absorption partly by protein misfolding. However, they do not necessarily lead to AKI and a possible genotype-phenotype correlation was not proposed. Furthermore, results confirm an uneven geographical and ethnic distribution of SLC22A12 variants; the p.L415_G417del mutation predominates in the Roma ethnic group in the Czech Republic.
Ames,
Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.
1981, Pubmed
Ames,
Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.
1981,
Pubmed
Anzai,
New insights into renal transport of urate.
2007,
Pubmed
Anzai,
Plasma urate level is directly regulated by a voltage-driven urate efflux transporter URATv1 (SLC2A9) in humans.
2008,
Pubmed
,
Xenbase
Augustin,
Identification and characterization of human glucose transporter-like protein-9 (GLUT9): alternative splicing alters trafficking.
2004,
Pubmed
,
Xenbase
Bell,
A microdissection library of the rat renal carcinoma gene region.
1995,
Pubmed
Davis,
Observations on serum uric acid levels and the risk of idiopathic Parkinson's disease.
1996,
Pubmed
Dinour,
Homozygous SLC2A9 mutations cause severe renal hypouricemia.
2010,
Pubmed
,
Xenbase
Dinour,
URAT1 mutations cause renal hypouricemia type 1 in Iraqi Jews.
2011,
Pubmed
,
Xenbase
Enomoto,
Molecular identification of a renal urate anion exchanger that regulates blood urate levels.
2002,
Pubmed
,
Xenbase
Erley,
Acute renal failure due to uric acid nephropathy in a patient with renal hypouricemia.
1989,
Pubmed
Glantzounis,
Uric acid and oxidative stress.
2005,
Pubmed
Graessler,
Association of the human urate transporter 1 with reduced renal uric acid excretion and hyperuricemia in a German Caucasian population.
2006,
Pubmed
Houlihan,
Variation in the uric acid transporter gene (SLC2A9) and memory performance.
2010,
Pubmed
Ichida,
Age and origin of the G774A mutation in SLC22A12 causing renal hypouricemia in Japanese.
2008,
Pubmed
Ichida,
Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion.
2004,
Pubmed
Iwai,
A high prevalence of renal hypouricemia caused by inactive SLC22A12 in Japanese.
2004,
Pubmed
Kousi,
Mutations in CLN7/MFSD8 are a common cause of variant late-infantile neuronal ceroid lipofuscinosis.
2009,
Pubmed
Lam,
A novel mutation of SLC22A12 gene causing primary renal hypouricemia in a patient with metabolic syndrome.
2008,
Pubmed
Matsuo,
Mutations in glucose transporter 9 gene SLC2A9 cause renal hypouricemia.
2008,
Pubmed
Naitoh,
Arginine vasopressin produces renal vasodilation via V2 receptors in conscious dogs.
1993,
Pubmed
Nakamura,
Concentration-dependent inhibitory effect of irbesartan on renal uric acid transporters.
2010,
Pubmed
,
Xenbase
Ouellet,
[Hereditary renal hypouricemia in a Caucasian patient: a case report and review of the literature].
2009,
Pubmed
Shima,
Recurrent EIARF and PRES with severe renal hypouricemia by compound heterozygous SLC2A9 mutation.
2011,
Pubmed
Sotgiu,
Serum uric acid and multiple sclerosis.
2002,
Pubmed
Stiburkova,
Novel homozygous insertion in SLC2A9 gene caused renal hypouricemia.
2011,
Pubmed
Stiburkova,
Novel mutations in xanthine dehydrogenase/oxidase cause severe hypouricemia: biochemical and molecular genetic analysis in two Czech families with xanthinuria type I.
2012,
Pubmed
Stiburkova,
Acute kidney injury in two children caused by renal hypouricaemia type 2.
2012,
Pubmed
Tabara,
Association of four genetic loci with uric acid levels and reduced renal function: the J-SHIPP Suita study.
2010,
Pubmed
Taniguchi,
A common mutation in an organic anion transporter gene, SLC22A12, is a suppressing factor for the development of gout.
2005,
Pubmed
Tasic,
Clinical and functional characterization of URAT1 variants.
2011,
Pubmed
Tin,
Genome-wide association study for serum urate concentrations and gout among African Americans identifies genomic risk loci and a novel URAT1 loss-of-function allele.
2011,
Pubmed
Vázquez-Mellado,
Molecular analysis of the SLC22A12 (URAT1) gene in patients with primary gout.
2007,
Pubmed
Wakida,
Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia.
2005,
Pubmed
,
Xenbase
Watanabe,
Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity.
2002,
Pubmed
de Lau,
Serum uric acid levels and the risk of Parkinson disease.
2005,
Pubmed
