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Case Reports
. 2018 Jun 29;18(1):210.
doi: 10.1186/s12887-018-1185-9.

A heterozygous variant in the SLC22A12 gene in a Sri Lanka family associated with mild renal hypouricemia

Dinesha Maduri Vidanapathirana  1 , Subashinie Jayasena  2 , Eresha Jasinge  2 , Blanka Stiburkova  3   4
Affiliations
Case Reports

A heterozygous variant in the SLC22A12 gene in a Sri Lanka family associated with mild renal hypouricemia

Dinesha Maduri Vidanapathirana et al. BMC Pediatr. .

Abstract

Background: Renal hypouricemia is a rare heterogeneous inherited disorder characterized by impaired tubular uric acid transport, reabsorption insufficiency and /or acceleration of secretion. The affected individuals are predisposed to nephrolithiasis and recurrent episodes of exercise-induced acute kidney injury. Type 1 is caused by dysfunctional variants in the SLC22A12 gene (URAT1), while type 2 is caused by defects in the SLC2A9 gene (GLUT9). To date, more than 150 patients with the loss-of-function mutations for the SLC22A12 gene have been found (compound heterozygotes and/or homozygotes), most of whom are Japanese and Koreans.

Case presentation: Herein, we report a nine year old Sri Lankan boy with renal hypouricemia (serum uric acid 97 μmol/L, fractional excretion of uric acid 33%).The sequencing analysis of SLC22A12 revealed a potentially deleterious missense variant c.1400C > T (p.T467 M, rs200104135) in heterozygous state. This variant has been previously identified in homozygous and/or compound heterozygous state with other causative SLC22A12 variant c.1245_1253del (p.L415_G417del) in Roma population.

Conclusions: This is the first identification of a family with mild renal hypouricemia1 associated to the p.T467 M variant. Detailed investigations of urate blood and urine concentrations in patients with unexplained hypouricemia are needed and renal hypouricemia should also be considered in patients other than those from Japan and/or Korea. Our finding confirms an uneven geographical and ethnic distribution of Romany prevalent SLC22A12 variant that need to be considered in Asian patients (population data Genome Aggregation Database: allele frequency in South Asia 0.007055, in East Asia 0.001330).

Keywords: Renal hypouricemia; SLC22A12; URAT1; Uric acid transporters.

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Conflict of interest statement

Consent for publication

Written informed consent was obtained from the parent of the patient for publication of this case report. A copy of the written consent is available for review by the editor of this journal.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Electropherograms showing part of the SLC2A9 and SLC22A12 gene sequence in family with renal hypouricemia. The figure show allelic variant p.V282I (c.757G > A) and p.P350L (c.1049C > T) in the SLC2A9 gene in wild-type (II.1), heterozygote (I.1, I.2) and recessive homozygote state (proband II.2, II.3); and dysfunctional SLC22A12 variant p.T467 M (c.1400C > T) causes renal hypouricemia in wild-type (I.2) and heterozygous state (I.1, II.1, proband II.2, II.3). Reference sequence: SLC2A9 NC_000011, region: 64114688..64126396, SLC22A12 NC_000004, region: 9436946..9650970
See this image and copyright information in PMC

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