Studies of Gene Abnormalities, Protein Abnormalities, and Their Phenotypes in Lysosomal Diseases.

溶酶体疾病中基因异常、蛋白质异常及其表型的研究。

• 批准号: 06670818
• 负责人: TANAKA Akemi
• 金额: $ 1.22万
• 依托单位: Osaka City 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: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670818/
• 关键词: beta-hexosaminidase; alphasubunit; betasubunit; Japanese major mutation; Tay-Sachs disease; Sandhoff disease; major mutation; 遺伝子解析; GM_2ガングリオシドーシス; β-hexosaminidase,α subunit; β-hexosaminidase,β subunit

beta-Hexosaminidase, alphasubunit :We found a mutation in the gene of beta-hexosaminidase, alphasubunit and named it Japanese major mutation in 1993. This mutant allele accounted for 80% of the alleles of 26 Japanese patients with infantile form of Tay-Sachs diseae. Moreover, the mutation is limited in Japanese and the carrier frequency of this mutant allele was one to 150 persons in Japan.The allele with the Japanase major mutation produced a stable but short mRNA with skipping of exon 6, and the alphasubunit polypeptide did not associete with the normal beta subunit polypeptide.beta-Hexosaminidase, betasubunit :The number of the patients with the betasubunit abnormalities is less than that with the alphasubunit abnormalities in Japan. The mutations in betasubunit gene reported so far are not so many compared with that of alphasubunit gene in the world.We characterized two mutatons of betasubunit gene in four Japanese patients with sandhoff disease (betasubunit gene abnormality). One of them was the same mutation which was found in a Japanese patient with a juvenile form of the disease. The reason why they show the different clinical pictures with the same genotype is being studied further.

β -己糖氨基酶：1993年在β -己糖氨基酶基因中发现了一个突变，并将其命名为日本重大突变。该突变等位基因占26例日本婴儿型Tay-Sachs病患者等位基因的80%。此外，该突变在日本是有限的，该突变等位基因在日本的携带频率为1 ~ 150人。具有Japanase主突变的等位基因产生一个稳定但短的mRNA，外显子6跳变，α亚单位多肽与正常的β亚单位多肽不相关。β -己糖氨酸酶，β亚单位：在日本，β亚单位异常的患者少于α亚单位异常的患者。与国际上报道的α亚基基因突变相比，目前报道的β亚基基因突变较少。我们在4名日本桑德霍夫病患者中发现了两个β亚单位基因突变（β亚单位基因异常）。其中一个基因突变与一名日本少年患者身上发现的基因突变相同。为什么相同的基因型表现出不同的临床表现，其原因还有待进一步研究。

项目成果

Mizuho Nagata et al.: "Prenatal Diagnosis of Lysosomal Diseases in the Recent Five Years" Rinsho Kagaku. 23. 221-227 (1994)

Mizuho Nagata等：“近五年溶酶体疾病的产前诊断”Rinsho Kagaku。

Akemi Tanaka et al.: "Molecular Genetics of Tay-Sachs Disease in Japan" J.of Inherited Metabolic Diseases. 17. 593-600 (1994)

Akemi Tanaka 等人：“日本泰萨克斯病的分子遗传学”J.of 遗传代谢疾病。

田中あけみ: "GM_2-ガングリオシドーシス(Tay-Sachs病)" 臨床DNA診断法(金原出版). 303-305 (1995)

Akemi Tanaka：“GM_2-神经节苷脂病（Tay-Sachs病）”临床DNA诊断方法（金原出版）303-305（1995）。

田中あけみ(共著): "臨床DNA診断法" 金原出版, 1134 (1995)

Akemi Tanaka（合著者）：《临床DNA诊断方法》Kanehara Publishing，1134（1995）

Akemi Tanaka: "Gaucher Disease, Tay-Sachs Disease, and Sandhoff Disease" Clinical Neuroscience. 12. 412-415 (1994)

Akemi Tanaka：“戈谢病、泰-萨克斯病和桑德霍夫病”临床神经科学。