酸性鞘磷脂酶:识别的九个小说突变意大利尼曼皮克B型患者和表征的体内功能在坐标系启动密码子。
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彼蒂毫克,里奇V, Guerci VI, Marcais C, Ciana G, Dardis, Gerin F, Stroppiano M,凡尼尔MT, Filocamo M, Bembi B
酸性鞘磷脂酶:识别的九个小说突变意大利尼曼皮克B型患者和表征的体内功能在坐标系启动密码子。
哼Mutat。2004年8月,24 (2):186 - 7。
- PubMed ID
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15241805 (在PubMed]
- 文摘
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尼曼皮克病(NPD)是一种常染色体隐性疾病由于溶酶体酸性鞘磷脂酶的赤字,导致胞内积累鞘磷脂。在目前的工作我们研究18 NPD B型患者,其中包括5个人提出一个中间表型的特点是不同程度的神经参与。我们确定了9个小说SMPD1基因的突变包括六个单基地变化c。2 t > G、c。96 g > A, c。308 t > C, C。674 t > C, C。732 g > C, C。841 g > A (p。M1_W32del, p。W32X, p。L103P, p。L225P, p。W244C p.A281T)和3 c移码突变。100 delc, c。565 dupc, c。575 dupc (p。G34fsX42, p。P189fsX1和p.P192fsX14)。 The novel c.2T>G (p.M1_W32del) mutation inactivates the first in-frame translation start site of the SMPD1 gene and in the homozygous status causes NPD type B indicating that in'vivo translation of wild type SMPD1 initiates from the first in-frame ATG. Moreover, the new c.96G>A (p.W32X) introduces a premature stop codon before the second in-frame ATG. As a consequence of either c.2T>G (p.M1_W32del) or c.96G>A (p.W32X), impaired translation from the first in-frame ATG results in a mild NPD-B phenotype instead of the severe phenotype expected for a complete deficiency of the enzyme, suggesting that when the first ATG is not functional, the second initiation codon (ATG33) still produces a fairly functional sphingomyelinase. Analysis of the patients'clinical and molecular data demonstrated that all five patients with the intermediate phenotype carried at least one severe mutation. No association between the onset of pulmonary symptoms and genotype was observed. Finally, the presence of c.96G>A (p.W32X), the most frequent allele among Italian NPD type B population, and c.1799G>C (p.R600P) as compound heterozygotes in association with severe mutations suggested a beneficial effect for both mutations.