Pediatric Nephrology

, Volume 19, Issue 7, pp 728–733 | Cite as

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

  • Fusako Komoda
  • Takashi SekineEmail author
  • Jun Inatomi
  • Atsushi Enomoto
  • Hitoshi Endou
  • Toshiyuki Ota
  • Takeshi Matsuyama
  • Tsutomu Ogata
  • Masahiro Ikeda
  • Midori Awazu
  • Koji Muroya
  • Isamu Kamimaki
  • Takashi Igarashi
Original Article


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.


Renal hypouricemia Urate transporter hURAT1 W258X mutation 



This work was supported by grants from the Japanese Ministry of Education, Science, Sports, and Culture (grant 13671101 and 15591089), The Kidney Foundation Japan (JFK 02–5), and The Morinaga Hoshi-kai.


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Copyright information

© IPNA 2004

Authors and Affiliations

  • Fusako Komoda
    • 1
  • Takashi Sekine
    • 1
    Email author
  • Jun Inatomi
    • 1
  • Atsushi Enomoto
    • 2
  • Hitoshi Endou
    • 2
  • Toshiyuki Ota
    • 3
  • Takeshi Matsuyama
    • 4
  • Tsutomu Ogata
    • 5
  • Masahiro Ikeda
    • 6
  • Midori Awazu
    • 7
  • Koji Muroya
    • 8
  • Isamu Kamimaki
    • 9
  • Takashi Igarashi
    • 1
  1. 1.Department of Pediatrics, Faculty of MedicineThe University of TokyoJapan
  2. 2.Department of Pharmacology and ToxicologyKyorin University School of MedicineTokyoJapan
  3. 3.Department of PediatricsHiroshima Prefectural HospitalHiroshimaJapan
  4. 4.Department of PediatricsFussa General HospitalTokyoJapan
  5. 5.Department of Endocrinology and MetabolismThe National Center for Child Health and Development Research InstituteTokyoJapan
  6. 6.Department of NephrologyTokyo Metropolitan Kiyose Children’s HospitalTokyoJapan
  7. 7.Department of PediatricsKeio University School of MedicineTokyoJapan
  8. 8.Department of PediatricsTokyo Dental College Ichikawa General HospitalChibaJapan
  9. 9.Department of PediatricsNational Saitama HospitalSaitamaJapan

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