The W258X mutation in SLC22A12 is the predominant cause of Japanese renal hypouricemia

Fusako Komoda, Takashi Sekine, Jun Inatomi, Atsushi Enomoto, Hitoshi Endou, Toshiyuki Ota, Takeshi Matsuyama, Tsutomu Ogata, Masahiro Ikeda, Midori Awazu, Koji Muroya, Isamu Kamimaki, Takashi Igarashi

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64 Citations (Scopus)

Abstract

Recently, a urate transporter, hURAT1 (human uric acid transporter 1) encoded by SLC22A12, was isolated from the human kidney. hURAT1 is presumed to play the central role in reabsorption of urate from glomerular filtrate. In the present study, we analyzed SLC22A12 in seven unrelated Japanese patients with renal hypouricemia whose serum level of urate was less than 1.0 mg/dl, and their family members. We performed direct DNA sequencing of the exon and exon-intron boundaries of SLC22A12 using genomic DNA. Six of the seven patients (86%) possess mutations in SLC22A12. In five patients, a homozygous G to A transition at nucleotide 774 within exon 4 of SLC22A12, which forms a stop codon (TGA) at codon 258 (TGG), was identified (W258X). In one patient, the C to T transition within exon 3, which changes threonine at codon 217 to methionine (T217 M), and the W258X mutation were found (compound heterozygote). Thus, among 12 mutational alleles in six patients, 11 were the W258X mutation (92%). Family members with the heterozygous W258X mutation (carriers) show relatively low levels of serum urate. The present study demonstrates that homozygous W258X mutation is the predominant genetic cause of idiopathic renal hypouricemia in Japanese patients.

Original languageEnglish
Pages (from-to)728-733
Number of pages6
JournalPediatric Nephrology
Volume19
Issue number7
DOIs
Publication statusPublished - 2004 Jul 1

Keywords

  • Renal hypouricemia
  • Urate transporter
  • W258X mutation
  • hURAT1

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

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  • Cite this

    Komoda, F., Sekine, T., Inatomi, J., Enomoto, A., Endou, H., Ota, T., Matsuyama, T., Ogata, T., Ikeda, M., Awazu, M., Muroya, K., Kamimaki, I., & Igarashi, T. (2004). The W258X mutation in SLC22A12 is the predominant cause of Japanese renal hypouricemia. Pediatric Nephrology, 19(7), 728-733. https://doi.org/10.1007/s00467-004-1424-1