International Porphyria Molecular Diagnostic Collaborative: an evidence-based database of verified pathogenic and benign variants for the porphyrias
International Porphyria Molecular Diagnostic Collaborative: an evidence-based database of verified pathogenic and benign variants for the porphyrias
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DOI：
10.1038/s41436-019-0537-7
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发表时间：
2019-11-01
影响因子：
8.8
通讯作者：
Desnick, Robert J.
中科院分区：
文献类型：
--
作者：
Chen, Brenden;Whatley, Sharon;Desnick, Robert J.
随着精确和基因组医学的出现，一个关键问题是疾病基因变异是致病的还是良性的。这是三个常染色体显性急性肝卟啉症（AHPs）的情况下，包括急性间歇性卟啉症，遗传性粪卟啉症，和杂色卟啉症，每一个导致的半正常酶活性的羟甲基胆烷合酶，粪卟啉原氧化酶，原卟啉原氧化酶，分别。到目前为止，还没有公共数据库记录引起卟啉病的变异体的可能致病性，更具体地说，没有具有生物化学和临床验证信息的AHPs。因此，我们认为，与欧洲卟啉病网络和美国国立卫生研究院/国家转化科学推进中心/国家糖尿病、消化和肾脏疾病研究所的国际合作（NIH/NCATS/NIDDK）-由卟啉病诊断专家赞助的卟啉病联盟正在建立一个在线数据库，该数据库将整理生物化学和临床证据，以验证已发表和新发现的卟啉病变体的致病性。AHP致病基因国际卟啉病分子诊断协作组织的总体目标是确定所有八种卟啉病的致病性和良性变异。在这里，我们描述了总体目标和初步的努力，以验证致病性和良性的变异，在各自的血红素生物合成基因引起的AHPs。
With the advent of precision and genomic medicine, a critical issue is whether a disease gene variant is pathogenic or benign. Such is the case for the three autosomal dominant acute hepatic porphyrias (AHPs), including acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, each resulting from the half-normal enzymatic activities of hydroxymethylbilane synthase, coproporphyrinogen oxidase, and protoporphyrinogen oxidase, respectively. To date, there is no public database that documents the likely pathogenicity of variants causing the porphyrias, and more specifically, the AHPs with biochemically and clinically verified information. Therefore, an international collaborative with the European Porphyria Network and the National Institutes of Health/National Center for Advancing Translational Sciences/ National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NCATS/NIDDK)-sponsored Porphyrias Consortium of porphyria diagnostic experts is establishing an online database that will collate biochemical and clinical evidence verifying the pathogenicity of the published and newly identified variants in the AHP-causing genes. The overall goal of the International Porphyria Molecular Diagnostic Collaborative is to determine the pathogenic and benign variants for all eight porphyrias. Here we describe the overall objectives and the initial efforts to validate pathogenic and benign variants in the respective heme biosynthetic genes causing the AHPs.