title: High frequency of SLC22A12 variants causing renal hypouricemia 1 in the Czech and Slovak Roma population; simple and rapid detection method by allele-specific polymerase chain reaction.
abstract: Renal hypouricemia is a rare heterogeneous inherited disorder characterized by impaired tubular uric acid transport with severe complications, such as acute kidney injury. Type 1 and 2 are caused by loss-of-function mutations in the SLC22A12 and SLC2A9 gene, respectively. A cohort of 881 randomly chosen ethnic Roma from two regions in Eastern Slovakia and two regions in the Czech Republic participated. Genomic DNA was isolated from buccal swabs and/or from blood samples. The c.1245_1253del and c.1400C>T genotypes were determined using polymerase chain reaction with allele-specific primers in a multiplex arrangement and/or direct sequencing of exon 7 and 9. Allele frequencies and genotypes were tested for Hardy-Weinberg equilibrium using the Chi-square test. 25 subjects were heterozygous and three were homozygous for the c.1245_1253del, while 92 subjects were heterozygous and two were homozygous for the c.1400C>T. Moreover, two participants were compound heterozygotes. Frequencies of the c.1245_1253del and c.1400C>T variants were 1.87 and 5.56 %, respectively. Our finding confirms an uneven geographical and ethnic distribution of SLC22A12 mutant variants. We found that the c.1245_1253del and c.1400C>T variants were present in the Czech and Slovak Roma population at unexpectedly high frequencies. Renal hypouricemia should be kept in mind during differential diagnostic on Roma patients with low serum uric acid concentrations.
authors.affiliation: Department of Biology, Faculty of Humanities and Natural Sciences, University of Presov, Presov, Slovakia.
authors.forename: Dana
authors.initials: D
authors.lastname: Gabrikova
authors.affiliation: Department of Biology, Faculty of Humanities and Natural Sciences, University of Presov, Presov, Slovakia.
authors.forename: Jarmila
authors.initials: J
authors.lastname: Bernasovska
authors.affiliation: First Faculty of Medicine, Institute of Inherited Metabolic Disorders, Charles University in Prague, Prague, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Sokolova
authors.affiliation: First Faculty of Medicine, Institute of Inherited Metabolic Disorders, Charles University in Prague, Prague, Czech Republic. stiburkova@revma.cz.|Institute of Rheumatology, Na Slupi 4, 128 50 Prague 2, Prague, Czech Republic. stiburkova@revma.cz.
authors.forename: Blanka
authors.initials: B
authors.lastname: Stiburkova
mesh_terms: D018153:Czech Republic; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D027361:Organic Anion Transporters / Q000235:genetics*; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D015499:Renal Tubular Transport, Inborn Errors / Q000235:genetics*; D012189:Retrospective Studies; D006178:Romani People / Q000235:genetics*; D018154:Slovakia; D014545:Urinary Calculi / Q000235:genetics*
chemical_list: D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human
keywords: Acute kidney injury; Renal hypouricemia; SLC22A12; URAT1