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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：
YOSHINO Makoto
金额：
$ 2.24万
依托单位：
Kurume University
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：
J Chromatogr B 792
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：
小児看護 28・4
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。