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Open AccessArticle

Clinical and Functional Characterization of a Novel URAT1 Dysfunctional Variant in a Pediatric Patient with Renal Hypouricemia

1
Institute of Rheumatology, Na Slupi 4, 128 50 Prague, Czech Republic
2
Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 2, 120 00 Prague, Czech Republic
3
Department of Rheumatology, First Faculty of Medicine, Charles University, Na Slupi 4, 128 50 Prague, Czech Republic
4
Department of Cell Biology, Faculty of Science, Charles University, Vinicna 7, 128 00 Prague, Czech Republic
5
Department of Pediatrics, University Hospital Brno, Medical Faculty of Masaryk University, Jihlavska 20, 625 00 Brno, Czech Republic
*
Author to whom correspondence should be addressed.
Appl. Sci. 2019, 9(17), 3479; https://doi.org/10.3390/app9173479
Received: 22 July 2019 / Revised: 16 August 2019 / Accepted: 20 August 2019 / Published: 23 August 2019
(This article belongs to the Special Issue Immunohistochemical Expression)
Renal hypouricemia (RHUC) is caused by an inherited defect in the main (reabsorptive) renal urate transporters, URAT1 and GLUT9. RHUC is characterized by decreased concentrations of serum uric acid and an increase in its excretion fraction. Patients suffer from hypouricemia, hyperuricosuria, urolithiasis, and even acute kidney injury. We report the clinical, biochemical, and genetic findings of a pediatric patient with hypouricemia. Sequencing analysis of the coding region of SLC22A12 and SLC2A9 and a functional study of a novel RHUC1 variant in the Xenopus expression system were performed. The proband showed persistent hypouricemia (67–70 µmol/L; ref. range 120–360 µmol/L) and hyperuricosuria (24–34%; ref. range 7.3 ± 1.3%). The sequencing analysis identified common non-synonymous allelic variants c.73G > A, c.844G > A, c.1049C > T in the SLC2A9 gene and rare variants c.973C > T, c.1300C > T in the SLC22A12 gene. Functional characterization of the novel RHUC associated c.973C > T (p. R325W) variant showed significantly decreased urate uptake, an irregular URAT1 signal on the plasma membrane, and reduced cytoplasmic staining. RHUC is an underdiagnosed disorder and unexplained hypouricemia warrants detailed metabolic and genetic investigations. A greater awareness of URAT1 and GLUT9 deficiency by primary care physicians, nephrologists, and urologists is crucial for identifying the disorder. View Full-Text
Keywords: SLC22A12; URAT1; hypouricemia; uric acid transporters; excretion fraction of uric acid SLC22A12; URAT1; hypouricemia; uric acid transporters; excretion fraction of uric acid
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MDPI and ACS Style

Stiburkova, B.; Bohata, J.; Minarikova, I.; Mancikova, A.; Vavra, J.; Krylov, V.; Doležel, Z. Clinical and Functional Characterization of a Novel URAT1 Dysfunctional Variant in a Pediatric Patient with Renal Hypouricemia. Appl. Sci. 2019, 9, 3479.

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