摘要
目的 探讨GM2 神经节苷脂沉积症发病的分子机理。方法 培养患者皮肤成纤维细胞 ,进行酶学、Western印迹杂交和免疫细胞化学分析。结果 4例GM2 神经节苷脂沉积症患者成纤维细胞内 β 氨基己糖苷酶 (hexosaminidase ,Hex)活性均显著降低 ,分别为正常人的 12 %、3 %、15 %和 6% ;两例Sandhoff病Hex成熟的α、β 亚基 (αm、βm)明显减少 ,但婴儿型与成年型减少的程度不同 ,1例Tay Sachs病只有αm明显减少 ,1例GM2 激活蛋白缺陷症αm、βm与正常人无差异 ;4例患者成纤维细胞内均有不同程度的GM2神经节苷脂的堆积。结论 GM2 神经节苷脂沉积症的发病与HEXA、HEXB、GM2 A基因突变引起相应蛋白表达、成熟障碍有关。
Objective: To study the molecular mechanism of GM2 gangliosidosis. Methods: The skin fibroblasts from 4 patients with GM2 gangliosidosis were subjected to culture. Enzyme activities assay, Western blot and immunocytochemical analysis were performed using the cultured fibroblasts. Results: The hexosaminidase (Hex) activities of 4 patients with GM2 gangliosidosis were significantly decreased. The activities were 12%, 3%, 15% and 6% of control values, respectively. Western blot analysis indicated that the amount of Hex mature α- and β-subunits (αm,βm) was decreased in cells from patients 2 and 3, but only decreased αm was found in patient 1, and both αm and βm were normal in cells from patient 4. Immunocytochemical analysis revealed the accumulated GM2 ganglioside in cells from patients 1-4. Conclusion: The pathogenesis of GM2 gangliosidosis was associated with deficiency of Hex αm and βm and GM2 activator caused by HEXA, HEXB and GM2A gene mutations.
出处
《中华医学遗传学杂志》
EI
CAS
CSCD
2003年第2期103-106,共4页
Chinese Journal of Medical Genetics
