Retrospective diagnosis of feline GM2 gangliosidosis variant 0 (Sandhoff-Like disease) in Japan: Possible spread of the mutant allele in the Japanese domestic cat population
Retrospective diagnosis of feline GM2 gangliosidosis variant 0 (Sandhoff-Like disease) in Japan: Possible spread of the mutant allele in the Japanese domestic cat population
复制标题
DOI：
10.1292/jvms.70.813
复制
发表时间：
2008-08-01
影响因子：
1.2
通讯作者：
Arai, Toshiro
中科院分区：
文献类型：
--
作者：
Yamato, Osamu;Hayashi, Daisuke;Arai, Toshiro
GM2神经节脂质中毒变异0（人类Sandhoff病）是一种溶酶体贮积病，由酸性-己糖氨基酶（Hex） a和Hex B同时缺乏引起，这是由于β亚基异常，这是这些酶分子中的常见成分。它由HEXB基因编码。在本研究中，对先前2例疑似猫桑德霍夫样病病例进行了回顾性诊断，采用DNA检测检测先前在另外2个日本家猫家庭的4只猫中发现的致病突变。酶分析还使用从受试者家庭收集的储存白细胞和血浆进行，以探讨酶诊断和携带者基因分型的有效性。DNA检测表明2例患者为纯合隐性突变。因此，在日本的4个不同地点发现了6只具有相同突变的猫，这表明该突变等位基因可能在日本家猫种群中广泛传播。在酶学分析中，用4-甲基伞形草酰n -乙酰- β - d -氨基葡萄糖作为底物测量的白细胞和血浆中的Hex A和Hex B活性，与正常猫和携带猫相比，在受感染的猫中可以忽略不计。然而，在正常猫和携带病毒的猫之间，酶活性有很大的重叠。因此，我们得出结论，酶分析对感染猫的诊断是有用的，但对携带者的基因分型是不可接受的。
GM2 gangliosidosis variant 0 (human Sandhoff disease) is a lysosomal storage disease caused by simultaneous deficiencies of acid beta-hexosaminidase (Hex) A and Hex B due to an abnormality of beta-subunit, a common component in these enzyme Molecules. which is coded by the HEXB gene. In the present study, a retrospective diagnosis was performed in 2 previous suspected cases of feline Sandhoff-like disease using a DNA test to detect the causative mutation identified previously in 4 cats in 2 other families of Japanese domestic cats. Enzymic analysis was also performed using stored leukocytes and plasma collected from the subject families in order to investigate the usefulness of enzymic diagnosis and genotyping of carriers. The DNA test Suggested that the 2 cases were homozygous recessive for the mutation. Consequently, 6 cats homozygous for the same mutation have been found in 4 separate locations of Japan, suggesting that this mutant allele may be spread widely in the Japanese domestic cat populations. In enzymic analysis, Hex A and Hex B activities in leukocytes and plasma measured using 4-methylumbelliferyl N-acetyl-beta-D-glucosaminide as a substrate were negligible in affected cats, compared with those in normal and carrier cats. However, there was a wide overlap in enzyme activity between normal and carrier cats. Therefore, it was concluded that enzymic analysis is useful for diagnosis of affected cats, but is not acceptable for genotyping of carriers.