title: The W258X mutation in SLC22A12 is the predominant cause of Japanese renal hypouricemia.
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 W258 X 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.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Fusako
authors.initials: F
authors.lastname: Komoda
authors.forename: Takashi
authors.initials: T
authors.lastname: Sekine
authors.forename: Jun
authors.initials: J
authors.lastname: Inatomi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Enomoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Endou
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ota
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikeda
authors.forename: Midori
authors.initials: M
authors.lastname: Awazu
authors.forename: Koji
authors.initials: K
authors.lastname: Muroya
authors.forename: Isamu
authors.initials: I
authors.lastname: Kamimaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Igarashi
mesh_terms: D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics; D007564:Japan; D007674:Kidney Diseases / Q000235:genetics* / Q000652:urine*; D008297:Male; D008659:Metabolic Diseases / Q000235:genetics* / Q000652:urine*; D009154:Mutation; D027361:Organic Anion Transporters / Q000235:genetics*; D027701:Organic Cation Transport Proteins; D017422:Sequence Analysis, DNA; D014527:Uric Acid / Q000652:urine*
chemical_list: D002352:Carrier Proteins; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; D014527:Uric Acid