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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023728%3A_____%2F19%3AN0000008" target="_blank" >RIV/00023728:_____/19:N0000008 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/19:00110982 RIV/00216208:11310/19:10400793 RIV/65269705:_____/19:00071215 RIV/00216208:11110/19:10400793 RIV/00064165:_____/19:10400793

Výsledek na webu

<a href="https://www.mdpi.com/2076-3417/9/17/3479" target="_blank" >https://www.mdpi.com/2076-3417/9/17/3479</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/app9173479" target="_blank" >10.3390/app9173479</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 mu mol/L; ref. range 120-360 mu mol/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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 mu mol/L; ref. range 120-360 mu mol/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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30226 - Rheumatology

Projekt

<a href="/cs/project/NV15-26693A" target="_blank" >NV15-26693A: Funkční studie alelických variant urátových transportérů v primární hyperurikémii a dně</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

APPLIED SCIENCES-BASEL

ISSN

2076-3417

e-ISSN

2076-3417

Svazek periodika

9

Číslo periodika v rámci svazku

17

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

8

Strana od-do

Art. Nr. 3479

Kód UT WoS článku

000488603600041

EID výsledku v databázi Scopus

2-s2.0-85072245054