期刊
BIOMEDICINES
卷 9, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines9111607
关键词
renal hypouricemia; URAT1; ethnic specificity; Roma
资金
- Czech Republic Ministry of Health [RVO 00023728, RVO VFN64165]
- Biobanks and Biomolecular Resources Research Infrastructure Consortium of Ministry of Education, Youth and Sports of the Czech Republic [BBMRICZ LM2018125]
Renal hypouricemia (RHUC) is a rare inherited disease caused by dysfunctional variants in URAT1 and GLUT9 genes. Patients with RHUC exhibit low serum uric acid concentration, high uric acid excretion, and symptoms such as urolithiasis. A study identified common dysfunctional URAT1 allelic variants in the Roma population, suggesting that the disease is underdiagnosed.
Renal hypouricemia (RHUC) is caused by an inherited defect in the main reabsorption system of uric acid, SLC22A12 (URAT1) and SLC2A9 (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 Kosice 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 SLC22A12 and SLC2A9 genes. Sequence analysis identified dysfunctional variants c.1245_1253del and c.1400C > T in the SLC22A12 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.
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