Acute kidney injury in two children caused by renal hypouricaemia type 2

Stibůrková, Blanka; Taylor, Judith; Marinaki, Anthony M.; Šebesta, Ivan

doi:10.1007/s00467-012-2174-0

Cited by 53 publications

(55 citation statements)

References 15 publications

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“…27,28 In addition, three cases from Czech Republic and United Kingdom concerning patients with RHUC2 were also lately published. 13,14 These reports and our findings suggest decreased awareness of RHUC outside of the Far East allows cases to go undetected. On the other hand, the high incidence of Far East RHUC is a reflection of the high allele frequency (2.30-2.37%) of the p.W258X in SLC22A12 among Japanese and Koreans 6,7 indicating a founder mutation on Asian continent.…”

Section: Discussionsupporting

confidence: 58%

“…9,10 Homozygous and/or compound heterozygous loss-of-function mutations in SLC2A9 responsible for severe hypouricemia, and in most patients complicated by nephrolithiasis and AKI have been described in a variety of ethnic groups: Israeli-Arab, Ashkenazi-Jewish, Japanese, Czech and United Kingdom. [11][12][13][14] The SLC22A12 gene is localized on chromosome 11q13. Ten exons encode two transcript variants of the URAT1 transporter (332 and 553 amino acids), which are specifically expressed on the apical membrane of the proximal tubules in the kidneys and in human vascular smooth muscle cells.…”

Section: Introductionmentioning

confidence: 99%

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Novel allelic variants and evidence for a prevalent mutation in URAT1 causing renal hypouricemia: biochemical, genetics and functional analysis

et al. 2013

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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.

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Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Novel allelic variants and evidence for a prevalent mutation in URAT1 causing renal hypouricemia: biochemical, genetics and functional analysis

et al. 2013

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“…Loss of function of GLUT9 results in hypouricemia, presumably as a consequence of both a reduced release of urate from the liver and poor reabsorption from the urine in the kidney. [186][187][188][189][190][191][192] Elevated levels of plasma urate have also been associated with hypertension, gout, and metabolic disease. A number of genome-wide association studies have identif ied polymorphisms in the hSLC2A9 gene.…”

Section: Glut2: Fanconi-bickel Syndromementioning

confidence: 99%

“…However, to date, few, if any, single nucleotide polymorphisms have been demonstrated to have direct effects on the function of the protein when it is expressed in vitro. [187][188][189][190][191][192] It is more likely that such mutations have subtle effects on levels of expression or interactions with other proteins in the cell.…”

Section: Glut2: Fanconi-bickel Syndromementioning

confidence: 99%

Structure of, and functional insight into the GLUT family of membrane transporters

Long¹,

Cheeseman²

2015

CHC

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This review examines the development of structure and function of the human GLUT proteins, gene family hSLC2A. These proteins are essential for moving the key metabolites, glucose, galactose, and fructose in and out of cells, as well as a number of other important substrates. Despite over five decades of research, it is still not fully understood how they work at the molecular level, although the recent publication of a crystal structure of GLUT1 sug-

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“…In addition, familial hypouricemia has also been described in patients harbouring homozygous or compound heterozygous mutations in the SLC2A9 gene, which encodes another key player in UA homeostasis, glucose transporter 9 (GLUT9; RHUC2). Patient ethnicity is diverse and includes Japanese, Chinese, Arab, Ashkenazi-Jewish, Anglo-Saxon, Greek, and Czech; to date, only few Caucasian families with a GLUT9 mutation have been reported [4][5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

A Novel Homozygous <b><i>SLC2A9</i></b> Mutation Associated with Renal-Induced Hypouricemia

et al. 2016

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Background: Hereditary renal hypouricemia (RHUC) is a genetically heterogenous disorder characterized by defective uric acid (UA) reabsorption resulting in hypouricemia and increased fractional excretion of UA; acute kidney injury (AKI) and nephrolithiasis are recognized complications. Type 1 (RHUC1) is caused by mutations in the SLC22A12 gene, whereas RHUC2 is caused by mutations in the SLC2A9 gene. Patient ethnicity is diverse but only few Caucasian families with an SLC2A9 mutation have been reported. Methods: The current report describes the clinical history, biochemical and molecular genetics findings of a native Austrian family with RHUC2. The propositus presented with 2 episodes of exercise-induced AKI and exhibited profound hypouricemia. Mutational screening of the SLC22A12 and SLC2A9 genes was performed. Results: The molecular analyses revealed the homozygous c.512G>A transition that leads to the p.Arg171His missense substitution in SLC2A9, confirming the diagnosis of RHUC2. Segregation study of the causal mutation revealed that the mother and elder sister were heterozygous carriers, whereas the younger sister was found to be homozygous. Conclusion: We report the identification of a novel mutation in SLC2A9 as the cause of RHUC2 in a native Austrian family. We show that glucose transporter 9 mutations cause severe hypouricemia in homozygous individuals and confirm the high risk of AKI in male individuals harbouring these mutations. In our literature review, we provide an overview of the putative underlying pathophysiology, potential renal complications, findings on kidney biopsy as well as potential long-time renal sequelae.

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Acute kidney injury in two children caused by renal hypouricaemia type 2

Cited by 53 publications

References 15 publications

Novel allelic variants and evidence for a prevalent mutation in URAT1 causing renal hypouricemia: biochemical, genetics and functional analysis

Novel allelic variants and evidence for a prevalent mutation in URAT1 causing renal hypouricemia: biochemical, genetics and functional analysis

Structure of, and functional insight into the GLUT family of membrane transporters

A Novel Homozygous <b><i>SLC2A9</i></b> Mutation Associated with Renal-Induced Hypouricemia

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