Renal Hypouricemia 1: Rare Disorder as Common Disease in Eastern Slovakia Roma Population

Renal hypouricemia (RHUC) is caused by an inherited defect in the main reabsorption system of uric acid, <i>SLC22A12</i> (URAT1) and <i>SLC2A9</i> (GLUT9). RHUC is characterized by a decreased serum uric acid concentration and an increase in its excreted fraction. Patients su...

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Autores principales:	Blanka Stiburkova, Jana Bohatá, Kateřina Pavelcová, Velibor Tasic, Dijana Plaseska-Karanfilska, Sung-Kweon Cho, Ludmila Potočnaková, Jana Šaligová
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	renal hypouricemia <i>SLC22A12</i> URAT1 ethnic specificity Roma Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f04b0b6447f749a39a7891cde2aa2bed
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spelling	oai:doaj.org-article:f04b0b6447f749a39a7891cde2aa2bed2021-11-25T16:49:34ZRenal Hypouricemia 1: Rare Disorder as Common Disease in Eastern Slovakia Roma Population10.3390/biomedicines91116072227-9059https://doaj.org/article/f04b0b6447f749a39a7891cde2aa2bed2021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1607https://doaj.org/toc/2227-9059Renal hypouricemia (RHUC) is caused by an inherited defect in the main reabsorption system of uric acid, <i>SLC22A12</i> (URAT1) and <i>SLC2A9</i> (GLUT9). RHUC is characterized by a decreased serum uric acid concentration and an increase in its excreted fraction. Patients suffer from hypouricemia, hyperuricosuria, urolithiasis, and even acute kidney injury. We report clinical, biochemical, and genetic findings in a cohort recruited from the Košice region of Slovakia consisting of 27 subjects with hypouricemia and relatives from 11 families, 10 of whom were of Roma ethnicity. We amplified, directly sequenced, and analyzed all coding regions and exon–intron boundaries of the <i>SLC22A12</i> and <i>SLC2A9</i> genes. Sequence analysis identified dysfunctional variants c.1245_1253del and c.1400C>T in the <i>SLC22A12</i> gene, but no other causal allelic variants were found. One heterozygote and one homozygote for c.1245_1253del, nine heterozygotes and one homozygote for c.1400C>T, and two compound heterozygotes for c.1400C>T and c.1245_1253del were found in a total of 14 subjects. Our result confirms the prevalence of dysfunctional URAT1 variants in Roma subjects based on analyses in Slovak, Czech, and Spanish cohorts, and for the first time in a Macedonian Roma cohort. Although RHUC1 is a rare inherited disease, the frequency of URAT1-associated variants indicates that this disease is underdiagnosed. Our findings illustrate that there are common dysfunctional URAT1 allelic variants in the general Roma population that should be routinely considered in clinical practice as part of the diagnosis of Roma patients with hypouricemia and hyperuricosuria exhibiting clinical signs such as urolithiasis, nephrolithiasis, and acute kidney injury.Blanka StiburkovaJana BohatáKateřina PavelcováVelibor TasicDijana Plaseska-KaranfilskaSung-Kweon ChoLudmila PotočnakováJana ŠaligováMDPI AGarticlerenal hypouricemia<i>SLC22A12</i>URAT1ethnic specificityRomaBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1607, p 1607 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	renal hypouricemia <i>SLC22A12</i> URAT1 ethnic specificity Roma Biology (General) QH301-705.5
spellingShingle	renal hypouricemia <i>SLC22A12</i> URAT1 ethnic specificity Roma Biology (General) QH301-705.5 Blanka Stiburkova Jana Bohatá Kateřina Pavelcová Velibor Tasic Dijana Plaseska-Karanfilska Sung-Kweon Cho Ludmila Potočnaková Jana Šaligová Renal Hypouricemia 1: Rare Disorder as Common Disease in Eastern Slovakia Roma Population
description	Renal hypouricemia (RHUC) is caused by an inherited defect in the main reabsorption system of uric acid, <i>SLC22A12</i> (URAT1) and <i>SLC2A9</i> (GLUT9). RHUC is characterized by a decreased serum uric acid concentration and an increase in its excreted fraction. Patients suffer from hypouricemia, hyperuricosuria, urolithiasis, and even acute kidney injury. We report clinical, biochemical, and genetic findings in a cohort recruited from the Košice region of Slovakia consisting of 27 subjects with hypouricemia and relatives from 11 families, 10 of whom were of Roma ethnicity. We amplified, directly sequenced, and analyzed all coding regions and exon–intron boundaries of the <i>SLC22A12</i> and <i>SLC2A9</i> genes. Sequence analysis identified dysfunctional variants c.1245_1253del and c.1400C>T in the <i>SLC22A12</i> gene, but no other causal allelic variants were found. One heterozygote and one homozygote for c.1245_1253del, nine heterozygotes and one homozygote for c.1400C>T, and two compound heterozygotes for c.1400C>T and c.1245_1253del were found in a total of 14 subjects. Our result confirms the prevalence of dysfunctional URAT1 variants in Roma subjects based on analyses in Slovak, Czech, and Spanish cohorts, and for the first time in a Macedonian Roma cohort. Although RHUC1 is a rare inherited disease, the frequency of URAT1-associated variants indicates that this disease is underdiagnosed. Our findings illustrate that there are common dysfunctional URAT1 allelic variants in the general Roma population that should be routinely considered in clinical practice as part of the diagnosis of Roma patients with hypouricemia and hyperuricosuria exhibiting clinical signs such as urolithiasis, nephrolithiasis, and acute kidney injury.
format	article
author	Blanka Stiburkova Jana Bohatá Kateřina Pavelcová Velibor Tasic Dijana Plaseska-Karanfilska Sung-Kweon Cho Ludmila Potočnaková Jana Šaligová
author_facet	Blanka Stiburkova Jana Bohatá Kateřina Pavelcová Velibor Tasic Dijana Plaseska-Karanfilska Sung-Kweon Cho Ludmila Potočnaková Jana Šaligová
author_sort	Blanka Stiburkova
title	Renal Hypouricemia 1: Rare Disorder as Common Disease in Eastern Slovakia Roma Population
title_short	Renal Hypouricemia 1: Rare Disorder as Common Disease in Eastern Slovakia Roma Population
title_full	Renal Hypouricemia 1: Rare Disorder as Common Disease in Eastern Slovakia Roma Population
title_fullStr	Renal Hypouricemia 1: Rare Disorder as Common Disease in Eastern Slovakia Roma Population
title_full_unstemmed	Renal Hypouricemia 1: Rare Disorder as Common Disease in Eastern Slovakia Roma Population
title_sort	renal hypouricemia 1: rare disorder as common disease in eastern slovakia roma population
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f04b0b6447f749a39a7891cde2aa2bed
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Renal Hypouricemia 1: Rare Disorder as Common Disease in Eastern Slovakia Roma Population

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