Molecular genetics of GM2-gangliosidosis AB variant: a novel mutation and expression in BHK cells.
Molecular genetics of GM2-gangliosidosis AB variant: a novel mutation and expression in BHK cells.
复制标题
GM2-神经节苷脂沉积症 AB 变体的分子遗传学：BHK 细胞中的新突变和表达。
DOI：
10.1007/bf00216446
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发表时间：
1993
期刊：
影响因子：
5.3
通讯作者：
Sandhoff,K
中科院分区：
文献类型：
--
作者：
Schröder,M;Schnabel,D;Hurwitz,R;Young,E;Suzuki,K;Sandhoff,K
GM 2激活剂是神经节苷脂GM 2的溶酶体降解所需的己糖胺酶A特异性糖脂结合蛋白。GM 2激活剂的遗传缺陷导致神经系统疾病，一种非典型形式的泰-萨克斯病（GM 2神经节苷脂沉积症变体AB）。在这里，我们描述了一个G506到C颠换（Arg 169到Pro）的mRNA的婴儿患者患有GM 2-神经节苷脂沉积症变异AB。使用聚合酶链反应扩增和直接测序技术，我们发现病人是纯合子的突变，而父母，如预期的那样，杂合子。BHK细胞转染突变体cDNA的构建体没有得到GM 2激活蛋白检测的Western印迹技术，而那些转染野生型cDNA构建体显示出显着水平的人GM 2激活蛋白。因此，脯氨酸对正常Arg 169的取代似乎导致突变型GM 2激活剂在翻译后加工步骤期间或到达溶酶体后过早降解。因此，GM 2神经节苷脂沉积症变体AB的表型的基础可能是由点突变引起的生理激活功能的失活或突变蛋白的不稳定性。
The GM2 activator is a hexosaminidase A-specific glycolipid-binding protein required for the lysosomal degradation of ganglioside GM2. Genetic deficiency of GM2 activator leads to a neurological disorder, an atypical form of Tay-Sachs disease (GM2 gangliosidosis variant AB). Here, we describe a G506to C transversion (Arg169to Pro) in the mRNA of an infantile patient suffering from GM2-gangliosidosis variant AB. Using the polymerase chain reaction amplification and direct-sequencing technique, we found the patient to be homozygous for the mutation, whereas the parents were, as expected, heterozygous. BHK cells transfected with a construct of mutant cDNA gave no GM2 activator protein detectable by the Western blotting technique, whereas those transfected by a wild-type cDNA construct showed a significant level of human GM2 activator protein. The substitution of proline for the normal Arg169therefore appears to result in premature degradation of the mutant GM2 activator, either during the post-translational processing steps or after reaching the lysosome. The basis for the phenotype of GM2 gangliosidosis variant AB may therefore be either inactivation of the physiological activator function by the point mutation or instability of the mutant protein.