A new syndrome associated with beta-glucocerebrosidase feficiency : morphological, biochemical, and mollecular genetic studies

与β-葡萄糖脑苷脂酶效率相关的新综合征：形态学、生化和分子遗传学研究

• 批准号: 05670563
• 负责人: UYAMA Eiichiro
• 金额: $ 1.28万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670563/
• 关键词: Gaucher-like disease; beta-glucocerebrosidase; hereditary valvular heart disease; hereditary deafness; a new syndrome; hereditary hydrocephalus; hereditary corneal opacities; hereditary leptomeningeal fibrosis; β-alucocerebrosidase欠損症; 新しい糖脂質蓄積症

Recently we reported peculiar unique hereidtary storage disorder entitled "A new syndrome associated with beta-glucocerebrosidase deficiency and a mosaic population of storage cells"(Acta Neurol Scand 1992 ; 86 : 407-420). In 1994, this disorder was classified as "MIM 231005 : Gaucher-like disease (Pseudo-Gaucher disease)" in 1lth edition of McKusick's "Mendelian Inheritance in Man" . In 1993, we performed genetic study using PCR to find a point mutation of the gene foe beta-glucocerebrosidase. However, we failed to detect point mutations such as Leu-444 to Pro, Asp-370 to Ser, Pro-415 to arg, Val-394 to Leu, Ser-364 to Thr, Cys-342 to Gly and Try-312 to Cys. In 1994, we performed enzyme analyzes in detail to exclude multiple enzyme deficiency, while the activity of 11 kind of enzymes were all normal except beta-glucocerebrosidase. However, we determined slight abnormak storage of lactosylceramide in addition to glucosylceramide in the spleen and liver of the proband. In 1995, we purified sphingolipid activator protein 2 (SAP-2) and compared with that of patients with type 2 Gaucher disease.However, there were no difference between the function and amount of SAP-2 in the proband and those of the latter. We suggest that this new syndrome may be a contiguous gene syndrome such as a new murine model due tomutant meraxin gene which contiguous to both glucocerebrosidase and thrombospondin 3.

最近，我们报道了一种独特的遗传性储存障碍，题为“与β-葡萄糖脑苷脂酶缺乏和储存细胞镶嵌群体相关的新综合征”（Acta Neurol Scand 1992；86：407-420）。 1994年，McKusick的《人类孟德尔遗传》第1l版将这种疾病分类为“MIM 231005：类戈谢病（Pseudo-Gaucher病）”。 1993年，我们利用PCR进行了基因研究，发现了β-葡萄糖脑苷脂酶基因的点突变。然而，我们未能检测到点突变，例如 Leu-444 变为 Pro、Asp-370 变为 Ser、Pro-415 变为 arg、Val-394 变为 Leu、Ser-364 变为 Thr、Cys-342 变为 Gly 以及 Try-312 变为 Cys。 1994年，我们进行了详细的酶分析，排除了多种酶的缺陷，除β-葡萄糖脑苷脂酶外，11种酶的活性均正常。然而，我们确定先证者的脾脏和肝脏中除了葡萄糖神经酰胺外，乳糖神经酰胺的储存也有轻微异常。 1995年，我们纯化了鞘脂激活蛋白2（SAP-2），并与2型戈谢病患者进行比较。但先证者与先证者SAP-2的功能和含量没有差异。我们认为这种新综合征可能是一种邻近基因综合征，例如由于与葡萄糖脑苷酶和血小板反应蛋白3邻近的meraxin基因突变而产生的新小鼠模型。

项目成果

Eiichiro Uyama: "Annual Review of Hydrocephalus Vol.11.1993" Neuron Pub Con,Tokyo, 2 (1995)

Eiichiro Uyama：“脑积水年度回顾 Vol.11.1993” Neuron Pub Con，东京，2 (1995)

Eiichiro Uyama: "Annual Review of Hydrocephalus Vo1.11.1993" Neuron Pub Co,Tokyo, 2 (1994)

Eiichiro Uyama：“脑积水年度回顾 Vo1.11.1993” Neuron Pub Co，东京，2 (1994)