Molecular analysis of the gene responsible for the hereditary disorders of urate transport with impairment of renal function

导致肾功能受损的遗传性尿酸盐转运障碍基因的分子分析

基本信息

  • 批准号:
    15591089
  • 负责人:
  • 金额:
    $ 2.37万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2003
  • 资助国家:
    日本
  • 起止时间:
    2003 至 2004
  • 项目状态:
    已结题

项目摘要

Recently, a urate transporter, hURATI (human uric acid transporter 1) encoded by SLC22A12, was isolated from the human kidney. In the present research project, 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. Among these, four patients developed acute renal failure after exercise. 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 SLC22AJ2. In five patients, a homozygous G-to-A transition at nucleotide 774 within exon 4 of SLC22A12, which will form a stop codon (TGA) at codon 258 (TGG), was identified (W258X). In one patient, the C-to-T transition within exon 3, which will change threonine at codon 217 to methionine (T217M), and the W258X mutation were found (compound heterozygote). Thus, among 12 mutational alleles in 6 patients, 11 were W258X mutation (92 %). Family members with the heterozygous W258X mutation (carriers) show relatively low levels of serum urate. We also analyzed SLC22A12 in two Korean patients with renal hypouricemia. In one patient W258X homozygous mutation was identified, and in the other W258X/R477H compound heterozygous mutation was noted. The present study demonstrates that W258X mutation is the predominant genetic cause of idiopathic renal hypouricemia in Japanese and Korean patients.
最近,一种由SLC22A12编码的尿酸转运蛋白hURATI (human uric acid transporter 1)从人类肾脏中分离出来。在本研究项目中,我们分析了7例血清尿酸水平低于1.0 mg/dl的日本肾性低尿酸血症患者及其家庭成员的SLC22A12。其中4例患者在运动后出现急性肾功能衰竭。我们使用基因组DNA对SLC22A12的外显子和外显子-内含子边界进行了直接DNA测序。7例患者中有6例(86%)具有SLC22AJ2突变。在5例患者中,鉴定出SLC22A12外显子4内核苷酸774处的纯合子G-to-A过渡,该过渡将在密码子258 (TGG)处形成停止密码子(TGA) (W258X)。1例患者发现外显子3内的C-to-T转位,将密码子217处的苏氨酸变为蛋氨酸(T217M),并发现W258X突变(复合杂合子)。因此,在6例患者的12个突变等位基因中,W258X突变11个(92%)。携带W258X杂合突变的家庭成员(携带者)血清尿酸水平相对较低。我们还分析了两例韩国肾性低尿酸血症患者的SLC22A12。在一名患者中发现W258X纯合突变,在另一名患者中发现W258X/R477H复合杂合突变。目前的研究表明,W258X突变是日本和韩国患者特发性肾性低尿酸血症的主要遗传原因。

项目成果

期刊论文数量(38)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The W258X mutation in SLC22A12 is the predominant cause of Japanese renal hypouricemia
  • DOI:
    10.1007/s00467-004-1424-1
  • 发表时间:
    2004-07-01
  • 期刊:
  • 影响因子:
    3
  • 作者:
    Komoda, F;Sekine, T;Igarashi, T
  • 通讯作者:
    Igarashi, T
Molccular and clinical studies of Dent's disease ----
Dent 病的分子和临床研究 ----
  • DOI:
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Matsuyama T;Sekine T. cl al.
  • 通讯作者:
    Sekine T. cl al.
Inatomi J, Sekine T, et al.: "Mutational and functional analysis of SLC4A4 in a patient with proximal renal tubular acidosis"European Journal of Physiology. (in press). (2004)
Inatomi J、Sekine T 等人:“近端肾小管酸中毒患者 SLC4A4 的突变和功能分析”欧洲生理学杂志。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Molecular and clinical studies of Dent's disease in Japan : biochemical examination and renal ultrasonography do not predict carrier state.
日本登特氏病的分子和临床研究:生化检查和肾脏超声检查不能预测携带者状态。
  • DOI:
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Matsuyama T;Awazu M;Oikawa T;Inatomi J;Sekine T;Igarashi T.
  • 通讯作者:
    Igarashi T.
Functional characterization of LMX1B mutations associated with nail-patella syndrome
  • DOI:
    10.1203/01.pdr.0000157674.63621.2c
  • 发表时间:
    2005-06-01
  • 期刊:
  • 影响因子:
    3.6
  • 作者:
    Sato, U;Kitanaka, S;Igarashi, T
  • 通讯作者:
    Igarashi, T
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SEKINE Takashi其他文献

水素チャージしたアルミ合金のミュオンスピン緩和測定
充氢铝合金的μ子自旋弛豫测量
  • DOI:
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    0
  • 作者:
    NINO Akihiro;SEKINE Takashi;SUGIYAMA Shigeaki;西村克彦
  • 通讯作者:
    西村克彦
Synthesis and Mechanical Properties of Silicon Nitride–Tungsten Carbide Composite Ceramics
氮化硅-碳化钨复合陶瓷的合成及力学性能

SEKINE Takashi的其他文献

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{{ truncateString('SEKINE Takashi', 18)}}的其他基金

Molecular analysis of the pathophysiology basis of nephrotic syndrome
肾病综合征病理生理基础的分子分析
  • 批准号:
    23591586
  • 财政年份:
    2011
  • 资助金额:
    $ 2.37万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Marketing Development of Home Electric Appliance in Japan, China, and Korea:from Viewpoint of Advantageous Position Dynamics
日中韩家电营销发展——基于优势地位动态的视角
  • 批准号:
    22330132
  • 财政年份:
    2010
  • 资助金额:
    $ 2.37万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Analysis of phosphorylation cascade of molecules expressed in podocyte as the pathophysiological basis of kidney diseases
足细胞表达分子磷酸化级联分析作为肾脏疾病的病理生理基础
  • 批准号:
    20591271
  • 财政年份:
    2008
  • 资助金额:
    $ 2.37万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of molecules responsible for the development of nephritic syndrome
鉴定导致肾病综合征发生的分子
  • 批准号:
    18591183
  • 财政年份:
    2006
  • 资助金额:
    $ 2.37万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Genetic analysis of transporters and channels related to urolithiasis or hydronephrosis
与尿石症或肾积水相关的转运蛋白和通道的遗传分析
  • 批准号:
    13671101
  • 财政年份:
    2001
  • 资助金额:
    $ 2.37万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The study toward the development of specific agonist and antagonist for the purinergic receptors in the kidney
肾脏嘌呤受体特异性激动剂和拮抗剂的开发研究
  • 批准号:
    08672623
  • 财政年份:
    1996
  • 资助金额:
    $ 2.37万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
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