Podrobný výpis o publikaci

STIBURKOVA, Blanka, Jana BOHATA, Iveta MINARIKOVA, Andrea MANCIKOVA, Jiri VAVRA, Vladimir KRYLOV a Zdeněk DOLEŽEL. Clinical and Functional Characterization of a Novel URAT1 Dysfunctional Variant in a Pediatric Patient with Renal Hypouricemia. Applied Sciences-Basel. BASEL: MDPI, 2019, roč. 9, č. 17, s. 1-8. ISSN 2076-3417. Dostupné z: https://dx.doi.org/10.3390/app9173479.

Další formáty: BibTeX LaTeX RIS

TY  - JOUR
ID  - 1570405
AU  - Stiburkova, Blanka - Bohata, Jana - Minarikova, Iveta - Mancikova, Andrea - Vavra, Jiri - Krylov, Vladimir - Doležel, Zdeněk
PY  - 2019
TI  - Clinical and Functional Characterization of a Novel URAT1 Dysfunctional Variant in a Pediatric Patient with Renal Hypouricemia
JF  - Applied Sciences-Basel
VL  - 9
IS  - 17
SP  - 1-8
EP  - 1-8
PB  - MDPI
SN  - 20763417
KW  - SLC22A12
KW  - URAT1
KW  - hypouricemia
KW  - uric acid transporters
KW  - excretion fraction of uric acid
UR  - http://dx.doi.org/10.3390/app9173479
L2  - http://dx.doi.org/10.3390/app9173479
N2  - 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.
ER  -

Základní údaje
Originální název	Clinical and Functional Characterization of a Novel URAT1 Dysfunctional Variant in a Pediatric Patient with Renal Hypouricemia
Autoři	STIBURKOVA, Blanka (203 Česká republika, garant), Jana BOHATA (203 Česká republika), Iveta MINARIKOVA (203 Česká republika), Andrea MANCIKOVA (203 Česká republika), Jiri VAVRA (203 Česká republika), Vladimir KRYLOV (203 Česká republika) a Zdeněk DOLEŽEL (203 Česká republika, domácí).
Vydání	Applied Sciences-Basel, BASEL, MDPI, 2019, 2076-3417.

Další údaje
Originální jazyk	angličtina
Typ výsledku	Článek v odborném periodiku
Obor	30217 Urology and nephrology
Stát vydavatele	Švýcarsko
Utajení	není předmětem státního či obchodního tajemství
WWW	URL
Impakt faktor	Impact factor: 2.474
Kód RIV	RIV/00216224:14110/19:00110982
Organizační jednotka	Lékařská fakulta
Doi	http://dx.doi.org/10.3390/app9173479
UT WoS	000488603600041
Klíčová slova anglicky	SLC22A12; URAT1; hypouricemia; uric acid transporters; excretion fraction of uric acid
Štítky	14110317, rivok
Příznaky	Mezinárodní význam, Recenzováno
Změnil	Změnila: Mgr. Tereza Miškechová, učo 341652. Změněno: 17. 2. 2020 10:52.

Anotace
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.

Anotace

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.