Efficacy of neutrophil non-muscle myosin heavy chain-IIA immunofluorescence analysis in determining the pathogenicity of MYH9 variants.
Efficacy of neutrophil non-muscle myosin heavy chain-IIA immunofluorescence analysis in determining the pathogenicity of MYH9 variants.
复制标题
中性粒细胞非肌肉肌球蛋白重链-IIA 免疫荧光分析在确定 MYH9 变异体致病性中的功效。
DOI：
10.1007/s00277-017-2972-3
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Kojima S.
中科院分区：
文献类型：
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作者：
Kunishima S;Yusuke O;Muramatsu H;Kojima D;Nagai N;Takahashi Y;Kojima S.
最近，新一代测序技术（NGS）的出现彻底改变了遗传疾病的基因研究和诊断方式，并出现了多篇关于血液病靶向测序的临床应用的文章[1,2]。应用NGS的主要挑战是难以确定未知意义变异的致病性。为了解决这个问题，传统的生化分析对于评估功能后果非常有用。我们在此报告了中性粒细胞非肌球蛋白重链iia （NMMHC-IIA）定位的免疫荧光分析在确定NGS鉴定的新型MYH9变体的致病性中的作用。一名12岁的日本男孩被临床诊断为先天性血小板减少症（血小板计数在50,000至100,000/μL之间），使用靶向测序平台[3]进行遗传性骨髓衰竭综合征（IBMFS）的遗传诊断。使用Agilent SureSelect定制探针和Illumina HiSeq2500下一代测序仪[3]对184个ibmfs相关基因进行分析。致病性鉴定
Dear Editor, The recent advent of the next-generation sequencing (NGS) has revolutionized the way of genetic research and diagnosis for inherited diseases and several articles have emerged on the clinical application of targeted sequencing of hematological disorders [1, 2]. The major challenge in the application of NGS is the difficulty in determining the pathogenicity of variants of unknown significance. To address this issue, conventional biochemical analyses can be highly useful for assessing the functional consequences. We here report the usefulness of an immunofluorescence analysis of neutrophil non-muscle myosin heavy chain-IIA (NMMHC-IIA) localization in determining the pathogenicity of a novel MYH9 variant identified by NGS.A 12-year-old Japanese boy who had been clinically diagnosed with congenital thrombocytopenia (platelet count ranged between 50,000 and 100,000/μL) was referred for a genetic diagnosis of inherited bone marrow failure syndromes (IBMFS) using a targeted sequencing platform [3]. A total of 184 IBMFS-associated genes were analyzed using Agilent SureSelect custom probes and an Illumina HiSeq2500 nextgeneration sequencer [3]. The pathogenicity of identified