Vanishing urate, acute kidney injury episodes and a homozygous SLC2A9 mutation

Androvitsanea, Ariadni; Stylianou, Kostas; Maragkaki, Eleftheria; Tzanakakis, Michael; Stratakis, Stavros; Petrakis, Ioannis; Giatzakis, Christophoros; Daphnis, Eugene

doi:10.1007/s11255-015-1005-1

Cited by 8 publications

(4 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, owing to their scarcity they are statistically difficult to detect, unless they have a very strong effect on disease risk. Rare knockout variants in the SLC2A9 and SLC22A12 genes that block the reuptake of urinary filtered uric acid cause hypouricaemia and exercise-induced kidney failure [26–29]. Examples of uncommon (1–2%), but not rare, genetic variants associated with gout are a coding variant in the ALDH16A1 gene in the Icelandic population (c.1580C > G; odds ratio, 3.7) [30], and the aforementioned knockout variant in the ABCG2 gene in the Japanese population (Q126X; odds ratio, 4.3) [24].…”

Section: Genetics Of Hyperuricaemia and Gout: Recent Discoveriesmentioning

confidence: 99%

The genetics of gout: towards personalised medicine?

Dalbeth

Stamp

Merriman

2017

BMC Med

View full text Add to dashboard Cite

Over the last decade, there have been major advances in the understanding of the genetic basis of hyperuricaemia and gout as well as of the pharmacogenetics of urate-lowering therapy. Key findings include the reporting of 28 urate-associated loci, the discovery that ABCG2 plays a central role on extra-renal uric acid excretion, the identification of genes associated with development of gout in the context of hyperuricaemia, recognition that ABCG2 variants influence allopurinol response, and the impact of HLA-B*5801 testing in reducing the prevalence of allopurinol hypersensitivity in high-risk populations. These advances, together with the reducing cost of whole genome sequencing, mean that integrated personalised medicine approaches may soon be possible in clinical practice. Genetic data may inform assessment of disease prognosis in individuals with hyperuricaemia or established gout, personalised lifestyle advice, selection and dosing of urate-lowering therapy, and prevention of serious medication adverse effects. In this article, we summarise the discoveries from genome-wide association studies and discuss the potential for translation of these findings into clinical practice.

show abstract

Section: Genetics Of Hyperuricaemia and Gout: Recent Discoveriesmentioning

confidence: 99%

The genetics of gout: towards personalised medicine?

Dalbeth

Stamp

Merriman

2017

BMC Med

View full text Add to dashboard Cite

show abstract

“…Most likely, this mutation originated on the Asian continent and expanded in the Japanese population either by a founder effect or by genetic drift or both [24]. Subsequently, RHUC cases from Israel, several European countries, Pakistan, and China have been reported [6,7,9,22,[25][26][27][28][29][30][31]. SLC22A12 variants c.1245_1253del; p.(L415_G417del) and c.1400C>T; p.(T467M) are the main cause of RHUC type 1 in Roma populations of the Czech Republic, Slovakia, and Spain, and appear with very high frequency in these populations, 5.6% and 1.9%, respectively [9,22,[32][33][34][35].…”

Section: Introductionmentioning

confidence: 99%

Pathogenic Variants of SLC22A12 (URAT1) and SLC2A9 (GLUT9) in Spanish Patients with Renal Hypouricemia: Founder Effect of SLC2A9 Variant c.374C>T; p.(T125M)

Perdomo-Ramirez,

Cordoba-Lanus,

Trujillo-Frias

et al. 2023

IJMS

View full text Add to dashboard Cite

Renal hypouricemia (RHUC) is a rare inherited disorder characterized by impaired urate reabsorption in the proximal tubule resulting in low urate serum levels and increased urate excretion. Some patients may present severe complications such as exercise-induced acute renal failure and nephrolithiasis. RHUC is caused by inactivating mutations in the SLC22A12 (RHUC type 1) or SLC2A9 (RHUC type 2) genes, which encode urate transporters URAT1 and GLUT9, respectively. In this study, our goal was to identify mutations associated with twenty-one new cases with RHUC through direct sequencing of SLC22A12 and SLC2A9 coding exons. Additionally, we carried out an SNPs-haplotype analysis to determine whether the rare SLC2A9 variant c.374C>T; p.(T125M), which is recurrent in Spanish families with RHUC type 2, had a common-linked haplotype. Six intragenic informative SNPs were analyzed using PCR amplification from genomic DNA and direct sequencing. Our results showed that ten patients carried the SLC22A12 mutation c.1400C>T; p.(T467M), ten presented the SLC2A9 mutation c.374C>T, and one carried a new SLC2A9 heterozygous mutation, c.593G>A; p.(R198H). Patients carrying the SLC2A9 mutation c.374C>T share a common-linked haplotype, confirming that it emerged due to a founder effect.

show abstract

“…The recent report of a 54-yearold Czech woman with a novel heterozygous missense mutation in the SLC2A9 gene, exhibiting low serum UA levels (1.16-1.78 mg/dl) and FE-UA of 17.7%, is in line with this observation; functional study of the identified mutation showed a significant decrease in urate uptake [7] . We have previously summarized the molecular and clinical features of all RHUC2 patients reported until 2014 [8] , and only a few new cases were published in the meanwhile [6,7,17,18] .…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

View full text Add to dashboard Cite

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.

show abstract

Vanishing urate, acute kidney injury episodes and a homozygous SLC2A9 mutation

Cited by 8 publications

References 5 publications

The genetics of gout: towards personalised medicine?

The genetics of gout: towards personalised medicine?

Pathogenic Variants of SLC22A12 (URAT1) and SLC2A9 (GLUT9) in Spanish Patients with Renal Hypouricemia: Founder Effect of SLC2A9 Variant c.374C>T; p.(T125M)

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

Contact Info

Product

Resources

About