title: Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia.
abstract: To date, 11 loss of function mutations in the human urate transporter 1 (hURAT1) gene have been identified in subjects with idiopathic renal hypouricemia. In the present studies we investigated the clinical features and the mutations in the hURAT1 gene in seven families with presecretory reabsorption defect-type renal hypouricemia and in one family with the postsecretory reabsorption defect type. Twelve affected subjects and 26 family members were investigated. Mutations were analyzed by PCR and the direct sequencing method. Urate-transporting activities of wild-type and mutant hURAT1 were determined by [14C]urate uptake in Xenopus oocytes. Mutational analysis revealed three previously reported mutations (G774A, A1145T, and 1639-1643 del-GTCCT) and a novel mutation (T1253G) in families with the presecretory reabsorption defect type. Neither mutations in the coding region of hURAT1 gene nor significant segregation patterns of the hURAT1 locus were detected in the postsecretory reabsorption defect type. All hURAT1 mutants had significantly reduced urate-transporting activities compared with wild type (P < 0.05; n = 12), suggesting that T1253G is a loss of function mutation, and hURAT1 is responsible for the presecretory reabsorption defect-type familial renal hypouricemia. Future studies are needed to identify a responsible gene for the postsecretory reabsorption defect-type familial renal hypouricemia.
authors.affiliation: Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto, Kumamoto 860-8556, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Wakida
authors.forename: Do Gia
authors.initials: DG
authors.lastname: Tuyen
authors.forename: Masataka
authors.initials: M
authors.lastname: Adachi
authors.forename: Taku
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nonoguchi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Oka
authors.forename: Osamu
authors.initials: O
authors.lastname: Ueda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tazawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kurihara
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yoneta
authors.forename: Hajime
authors.initials: H
authors.lastname: Shimada
authors.forename: Takashi
authors.initials: T
authors.lastname: Oda
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsuo
authors.forename: Makoto
authors.initials: M
authors.lastname: Hosoyamada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Endou
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
authors.forename: Kimio
authors.initials: K
authors.lastname: Tomita
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kitamura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D027361:Organic Anion Transporters / Q000235:genetics*; D027701:Organic Cation Transport Proteins; D015499:Renal Tubular Transport, Inborn Errors / Q000235:genetics*; D014527:Uric Acid / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; D014527:Uric Acid