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首页> 外文期刊>British Journal of Haematology >Multiple in silico tools predict phenotypic manifestations in congenital thrombotic thrombocytopenic purpura
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Multiple in silico tools predict phenotypic manifestations in congenital thrombotic thrombocytopenic purpura

机译：多种计算机软件工具可预测先天性血栓性血小板减少性紫癜的表型表现

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Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare, recessively inherited genetic disorder with varying clinical presentation that is caused by ADAMTS13 mutations. Several studies have found limited associations between ADAMTS13 mutations and cTTP phenotype. The use of in silico tools that examine multiple mutation characteristics may better predict phenotype. We analysed 118 ADAMTS13 mutations found in 144 cTTP patients reported in the literature and examined associations of several mutation characteristics, including N-terminal proximity, the evolutionary conservation of the affected amino acid position, as well as amino acid charge/phosphorylation and genetic codon usage to disease phenotype. Structure-altering mutations were examined for their impact on ADAMTS13 function based on existing ADAMTS13 crystallographic data (AA 77-685). Our in silico data indicate that: (i) The position of the mutation in the N- or C-terminus, (ii) evolutionary conservation and (iii) codon usage of the affected mutation position are associated with disease parameters, such as age of onset, organ damage and fresh frozen plasma prophylaxis. In conclusion, the usage of multiple in silico tools presents a promising strategy in refining predictions for the diverse presentation of cTTP. Enhancing our utilization of in silico tools to find genotype-phenotype associations will create better-tailored approaches for individual patient treatment. ? 2013 Blackwell Publishing Ltd.
机译：先天性血栓性血小板减少性紫癜（cTTP）是一种罕见的，隐性遗传性遗传疾病，由ADAMTS13突变引起，临床表现各异。几项研究发现，ADAMTS13突变与cTTP表型之间的关联有限。使用计算机软件检查多个突变特征可以更好地预测表型。我们分析了在文献中报道的144例cTTP患者中发现的118个ADAMTS13突变，并研究了多个突变特征的关联，包括N末端邻近性，受影响氨基酸位置的进化保守性，氨基酸电荷/磷酸化和遗传密码子使用疾病表型。根据现有的ADAMTS13晶体学数据（AA 77-685），检查了改变结构的突变对ADAMTS13功能的影响。我们的计算机模拟数据表明：（i）突变在N或C端的位置，（ii）进化保守性和（iii）受影响突变位置的密码子使用与疾病参数（例如年龄）相关。起病，器官损害和新鲜冷冻血浆预防。综上所述，使用多种计算机软件工具可提供一种有前途的策略，可以改进cTTP的多种表示形式的预测。加强我们对计算机工具的利用，以发现基因型与表型之间的关联，将为个体患者的治疗提供量身定制的方法。 ？ 2013布莱克威尔出版有限公司

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