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

Author:

Wakida Naoki12,Tuyen Do Gia1,Adachi Masataka1,Miyoshi Taku1,Nonoguchi Hiroshi1,Oka Toshiaki3,Ueda Osamu3,Tazawa Masahiro4,Kurihara Satoshi5,Yoneta Yoshitaka6,Shimada Hajime6,Oda Takashi7,Kikuchi Yuichi7,Matsuo Hirotaka8,Hosoyamada Makoto9,Endou Hitoshi9,Otagiri Masaki2,Tomita Kimio1,Kitamura Kenichiro1

Affiliation:

1. Departments of Nephrology (N.W., D.G.T., M.A., T.M., H.N., K.T., K.K.), Kumamoto 860-8556, Japan;

2. Biopharmaceutics (N.W., M.O.), Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Kumamoto 860-8556, Japan;

3. Department of Pediatrics, Sapporo Tokushukai Hospital (T.Ok., O.U.), Hokkaido 003-0021, Japan;

4. Department of Pediatrics, Fujita Health University School of Medicine (M.T.), Aichi 470-1192, Japan;

5. Department of Medicine, Kasukabe Shuwa Hospital (S.K.), Saitama 344-0038, Japan;

6. Department of Medicine, Kitasato Medical Center Hospital (Y.Y., H.S.), Saitama 364-0026, Japan;

7. Second Department of Internal Medicine (T.Od., Y.K.), Saitama 359-0042, Japan;

8. First Department of Physiology (H.M.), National Defense Medical College, Saitama 359-0042, Japan;

9. Department of Pharmacology and Toxicology, Kyorin University School of Medicine (M.H., H.E.), Tokyo 181-8611, Japan

Abstract

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.

Publisher

The Endocrine Society

Subject

Biochemistry, medical,Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3