功能体外表征14 SMPD1突变在意大利病人受到尼曼皮克B型疾病。
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Dardis, Zampieri年代,Filocamo M, Burlina, Bembi B,彼蒂毫克
功能体外表征14 SMPD1突变在意大利病人受到尼曼皮克B型疾病。
哼Mutat。2005年8月,26 (2):164。
- PubMed ID
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16010684 (在PubMed]
- 文摘
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尼曼皮克病(NPD)是一种常染色体隐性溶酶体储存障碍造成的酸性鞘磷脂酶的缺乏活动由于SMPD1基因的突变。我们功能特点三个小说SMPD1突变和11个已经发表在意大利的人口。突变等位基因研究的酶活性和蛋白质加工是暂时性的转染COS-1细胞。c。96 g > A, c。100 delg, c。565 dupc, c。575 dupc (p。W32X, p。G34fsX42, p。P189fsX1和p.P192fs14)等位基因表达没有免疫反应性的蛋白质,因此没有酶活性。相比之下,细胞转染与突变体c。308 t > C, C。389 t > C, C。674 t > C, C。732 g > C, C。841 g > A, c。1687G>A, c.1799G>A, and c.1799G>C (p.L103P, p.V130A, p.L225P, p.W244C, p.A281T, p.D563Y, p.R600H, p.R600P) expressed protein levels comparable to wild-type ASM expressing cells. Only three of these constructs, c.389T>C, c.1687G>A, and c.1799G>A (p.V130A, p.D563Y, p.R600H), retained residual activity while the other five expressed very low or no enzyme activity. As expected, the c.1669underscore;1670delGT (p.V557fsX18) mutant expressed a completely inactive truncated protein. Interestingly, the c.2T>G (p.M1_W32del) mutant expressed 26.9% of the wild type activity, even though no ASM protein was detected by Western blot analysis, suggesting that the amount of produced enzyme is below detection levels. The results presented in this study are consistent with the wide phenotype variability found in NP type B patients and provide valuable insights into the molecular basis of the disease.