Clinical and Functional Characterization of a Novel URAT1 Dysfunctional Variant in a Pediatric Patient with Renal Hypouricemia
The result's identifiers
Result code in 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>
Alternative codes found
RIV/00216224:14110/19:00110982 RIV/00216208:11310/19:10400793 RIV/65269705:_____/19:00071215 RIV/00216208:11110/19:10400793 RIV/00064165:_____/19:10400793
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Clinical and Functional Characterization of a Novel URAT1 Dysfunctional Variant in a Pediatric Patient with Renal Hypouricemia
Original language description
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.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30226 - Rheumatology
Result continuities
Project
<a href="/en/project/NV15-26693A" target="_blank" >NV15-26693A: Function study of allelic variants of urate transporters in primary hyperuricemia and gout</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
APPLIED SCIENCES-BASEL
ISSN
2076-3417
e-ISSN
2076-3417
Volume of the periodical
9
Issue of the periodical within the volume
17
Country of publishing house
CH - SWITZERLAND
Number of pages
8
Pages from-to
Art. Nr. 3479
UT code for WoS article
000488603600041
EID of the result in the Scopus database
2-s2.0-85072245054