A heterozygous variant in the SLC22A12 gene in a Sri Lanka family associated with mild renal hypouricemia
Abstrakt
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 mu mol/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).