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Mutations in Human Urate Transporter 1 Gene in Presecretory Reabsorption Defect Type of Familial Renal Hypouricemia

2005; Oxford University Press; Volume: 90; Issue: 4 Linguagem: Inglês

10.1210/jc.2004-1111

1945-7197

Naoki Wakida, Đỗ Gia Tuyển, Masataka Adachi, Taku Miyoshi, Hiroshi Nonoguchi, Toshiaki Oka, Osamu Ueda, Masahiro Tazawa, Satoshi Kurihara, Yoshitaka Yoneta, Hajime Shimada, Oda T, Yuichi Kikuchi, Hirotaka Matsuo, Makoto Hosoyamada, Hitoshi Endou, Masaki Otagiri, Kimio Tomita, Kenichiro Kitamura,

Muscle and Compartmental Disorders

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.