Gindele Réka, Kerényi Adrienne, Kállai Judit, Pfliegler György, Schlammadinger Ágota, Szegedi István, Major Tamás, Szabó Zsuzsanna, Bagoly Zsuzsa, Kiss Csongor, Kappelmayer János, Bereczky Zsuzsanna
Division of Clinical Laboratory Science and Specialist Clinical Hemostasis Laboratory, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
Life (Basel). 2021 Mar 5;11(3):202. doi: 10.3390/life11030202.
Diagnosis of rare bleeding disorders is challenging and there are several differential diagnostics issues. Next-generation sequencing (NGS) is a useful tool to overcome these problems. The aim of this study was to demonstrate the usefulness of molecular genetic investigations by summarizing the diagnostic work on cases with certain bleeding disorders. Here we report only those, in whom NGS was indicated due to uncertainty of diagnosis or if genetic confirmation of initial diagnosis was required. Based on clinical and/or laboratory suspicion of von Willebrand disease (vWD, = 63), hypo-or dysfibrinogenemia ( = 27), hereditary hemorrhagic telangiectasia (HHT, = 10) and unexplained activated partial thromboplastin time (APTT) prolongation ( = 1), NGS using Illumina platform was performed. Gene panel covered 14 genes (, , , , , , , , , , , , and ) selected on the basis of laboratory results. We identified forty-seven mutations, = 29 (6 novel) in vWD, = 4 mutations leading to hemophilia A, = 10 (2 novel) in fibrinogen disorders, = 2 novel mutations in HHT phenotype and two mutations (1 novel) leading to prekallikrein deficiency. By reporting well-characterized cases using standardized, advanced laboratory methods we add new pieces of data to the continuously developing "bleeding disorders databases", which are excellent supports for clinical patient management.
罕见出血性疾病的诊断具有挑战性，存在多个鉴别诊断问题。新一代测序（NGS）是克服这些问题的有用工具。本研究的目的是通过总结某些出血性疾病病例的诊断工作来证明分子遗传学研究的实用性。在此我们仅报告那些因诊断不确定或需要对初步诊断进行基因确认而进行NGS检测的病例。基于临床和/或实验室怀疑患有血管性血友病（vWD，n = 63）、低纤维蛋白原血症或异常纤维蛋白原血症（n = 27）、遗传性出血性毛细血管扩张症（HHT，n = 10）以及不明原因的活化部分凝血活酶时间（APTT）延长（n = 1），使用Illumina平台进行了NGS检测。基因 panel 涵盖了根据实验室结果选择的14个基因（F8、F9、VWF、FGA、FGB、FGG、SERPINC1、SERPINF2、PROCR、THBD、ADAMTS13、ENG、ACVRL1 和 KLKB1）。我们鉴定出47个突变，其中vWD中有29个（6个为新突变），4个导致血友病A的突变，纤维蛋白原疾病中有10个（2个为新突变），HHT表型中有2个新突变，以及2个导致前激肽释放酶缺乏的突变（1个为新突变）。通过使用标准化的先进实验室方法报告特征明确的病例，我们为不断发展的“出血性疾病数据库”增添了新的数据，这些数据库对临床患者管理提供了出色的支持。
