Analysis of Mutations in the Urate Transporter 1 (URAT1) Gene of Japanese Patients with Hypouricemia in Northern Japan and Review of the Literature

Abstract

Background. Renal hypouricemia is an autosomal recessive disorder resulting from inactivating mutations in the urate transporter 1 (URAT1) encoded by SLC22A12. To date, 10 mutations have been identified and W258X in the URAT1 gene is the predominant cause in middle to southwestern Japan. However, it is still unclear whether there is a regional specific distribution of mutations in northern Japan. In this study, we analyzed mutations in the URAT1 gene of five Japanese patients with renal hypouricemia in northern Japan. Methods. Peripheral blood mononuclear cells were isolated from patients with hypouricemia and healthy control subjects. A mutation analysis of the URAT1 gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. Results. We identified two mutations. These mutations [c.269G>A (R90H) and c.774G>A (W258X)] have been reported in Japanese patients. Two of five patients were homozygotes (W258X), two carried single heterozygous mutations (W258X), and the remaining one was a compound heterozygote (R90H and W258X). Conclusions. Our study suggests that there is no regional different distribution of the URAT1 genetic mutations in Japanese with renal hypouricemia.