A study on Presymptomatic recognition and prevention of late-onset ornithine transcarbamylase deficiency in male

男性迟发性鸟氨酸转氨甲酰酶缺乏症的症状前识别和预防研究

基本信息

  • 批准号:
    15591148
  • 负责人:
  • 金额:
    $ 2.24万
  • 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 2005
  • 项目状态:
    已结题

项目摘要

1)Mutational analysis of ornithine transcarbamylase(OTC)gene in 14 male patients with late-onset presentation from 10 discrete families revealed 10 patients from 7 families carried the R40H mutation, 2 patients from 2 families harbored the Y55D mutation and 2 patients from one family had the R277W mutation. These observations were unique in that these patients had the common mutations, in contrast to patients with neonatal onset, who invariably have private mutations.2)The Y55D and R277W mutations were transmitted exclusively from maternal side to their offspring. The incidence of the R40H mutation generated de novo was estimated to be not more than 12%. Mother-to-child transmission of the R40H gene was observed in 10 pairs, while father-to daughter transmission was found only in 3 pairs. A higher reproductive loss in hemizygous male patients than in heterozygous females may have contributed to this difference. Two heterozygous female developed symptomatic diseases, indicating that prognosis of heterozygous females carrying this mutation is not always fair.3)Development of simple method to detect the 3 mutations was studied. Detection of the mutation by means of difference in Tm values of PCR products was first tried but reproducibility was poor. In stead, a multiplex PCR method is now being developed.4)Mutational analysis in 3 male patients with neonatal onset revealed discrete, novel mutations in each family.5)Analysis of prognostic factor of life revealed that concentration of lysine and the other 8 amino acids in plasma were found to be significant determinants.6)It was proved that an early diagnosis and conventional, though appropriate, intervention could improve outcome of a hyperammonemic crisis in the late-onset male patients.
1)对来自10个离散家系的14例晚发型男性患者进行了鸟氨酸转氨酶(OTC)基因突变分析,发现7个家系10例携带R40H突变,2个家系2例携带Y55D突变,1个家系2例携带R277W突变。这些观察结果的独特之处在于,这些患者具有共同的突变,而新生儿发病的患者总是有私人突变。2)Y55D和R277W突变仅从母方传递给他们的后代。据估计,R40H突变从头产生的发生率不超过12%。R40H基因母婴传播有10对,父女传播仅3对。半合子男性患者的生殖损失高于杂合子女性患者,这可能是造成这种差异的原因之一。两名杂合子女性出现症状性疾病,表明携带该突变的杂合子女性的预后并不总是公平的。3)研究了检测这3种突变的简便方法。首次尝试利用聚合酶链式反应产物的TM值差异来检测突变,但重复性较差。4)对3名新生儿发病的男性患者进行突变分析,发现每个家系都有离散的、新的突变。5)对预后因素的分析表明,血浆中赖氨酸和其他8种氨基酸的浓度是重要的决定因素。6)研究证明,早期诊断和常规的干预措施虽然适当,但可以改善晚发男性患者高氨血症危象的预后。

项目成果

期刊论文数量(64)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Effect of supplementation with L-carnitine at a small dose on acycarnitine profiles in serum and urine andthe renal handling of acylcarnitines in a patient withmultiple acylcoenzyme A dehydrogenation defect.
补充小剂量左旋肉碱对患有多种酰基辅酶 A 脱氢缺陷的患者的血清和尿液中酰基肉碱谱以及酰基肉碱肾脏处理的影响。
  • DOI:
  • 发表时间:
    2003
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Yoshino M;Tokunaga Y;Watanabe Y;Yoshida I;Sakaguchi M;Hata I;Shigematsu Y;Kimura M;Yamaguchi S.
  • 通讯作者:
    Yamaguchi S.
芳野 信: "今日の小児治療指針第13版(尿素サイクル異常症)"医学書院. 690 (2003)
Shin Yoshino:“当今儿科治疗指南第 13 版(尿素循环障碍)”Igaku Shoin 690 (2003)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
小児の検査とインフォームドコンセント
儿科测试和知情同意
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Harada E;Nishiyori A;Tokunaga Y;Watanabe Y;Kuriya N;Kumashiro R;Kuno T;Kuromaru R;Hirose S;Ichikawa K;Yoshino M;芳野 信
  • 通讯作者:
    芳野 信
Informed consent on laboratory studies in children.
儿童实验室研究的知情同意书。
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Watanabe Y;Harada H;Yoshino M;Yoshino M.
  • 通讯作者:
    Yoshino M.
Omithine transcarbamylase deficiency : recurrence of mutations associated with late-onset disease in maple patients in unrelated families and phenotypic variability.
鸟氨酸转氨甲酰酶缺乏症:与无关家族的枫树患者迟发性疾病相关的突变复发和表型变异。
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Watanabe Y;Harada H;Yoshino M.
  • 通讯作者:
    Yoshino M.
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YOSHINO Makoto其他文献

YOSHINO Makoto的其他文献

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{{ truncateString('YOSHINO Makoto', 18)}}的其他基金

A Study on Molecular Epidemiology and Prevention of Onset of Late-onset Ornithine Transcarbamylase Deficiency in Male Patients
男性迟发性鸟氨酸转氨甲酰酶缺乏症的分子流行病学及预防研究
  • 批准号:
    12670796
  • 财政年份:
    2000
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular Mechanism of Localization of the Mutant Ornithine Transcarbamylase to Mitochondrial Compartment
突变型鸟氨酸转氨甲酰酶定位于线粒体区室的分子机制
  • 批准号:
    09670854
  • 财政年份:
    1997
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular Mechanism of Late Onset Type of Ornithine Transcarbamylase Deficiency in Males
男性迟发型鸟氨酸转氨甲酰酶缺乏症的分子机制
  • 批准号:
    06670843
  • 财政年份:
    1994
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
A study on the mutations at the phynylalanine hydroxylase gene among the Japanese population
日本人群中苯丙氨酸羟化酶基因突变的研究
  • 批准号:
    02670467
  • 财政年份:
    1990
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
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