摘要目的 评估靶向二代基因测序(NGS)在先天性贫血诊断中的价值.方法 设计含217个先天性贫血相关致病基因的NGS基因组合——BDHAP-2014,对2014年8月至2017年7月连续就诊的临床怀疑诊断先天性贫血的患者进行NGS检测和亲代验证.结果 共纳入46例患者,临床疑诊分别为范可尼贫血(FA)11例、先天性红细胞生成异常性贫血(CDA)8例、先天性铁粒幼红细胞性贫血(CSA)6例、先天性溶血性贫血(CHA)12例、先天性角化不良(DC)1例、铁剂难治性缺铁性贫血(IR-IDA)4例及未明原因的血细胞减少(Uc)4例.经靶向NGS检测,28例(60.9%)患者明确了诊断和(或)分型,累及12个基因共44种致病性突变.其中26例(56.5%)基因诊断结果与临床疑诊相符,包括FA(5/11,45.5%)、CSA(6/6,100.0%)、CDA(3/8,37.5%)及CHA(12/12,100.0%);2例(4.3%)患者的基因诊断结果与临床疑诊不一致,依据NGS纠正了诊断,包括1例DC和1例家族性噬血细胞性淋巴组织细胞增生症(FHL);12例CHA依据基因检查结果进一步明确了溶血类型.18例(39.1%)患者未明确致病基因,最终未能明确诊断.结论 NGS对临床疑诊先天性贫血患者具有重要的诊断价值,可为临床治疗选择提供依据.

abstractsObjective To evaluate the impact of the targeted next-generation sequencing (NGS) assay for difficult congenital anemias. Methods Blood Disease Hospital Anemia Panel 2014 (BDHAP-2014) including 217 known genes of congenital anemias was developed. NGS and parental verification were performed for patients who were suspected diagnosed with congenital anaemia from August 2014 to July 2017.Results A total of 46 patients were enrolled in this study,the clinical suspection were 11 cases Fanconi anemia (FA), 8 cases congenital dyserythropoietic anemia (CDA), 6 cases congenital sideroblast anemia (CSA),12 cases congenital hemolytic anemia (CHA),1 case dyskeratosis congenital (DC),4 cases iron-refractory iron deficiency anemia and 4 cases unexplained cytopenia (Uc),respectively.28(60.9%) of 46 patients became confirmed cases after targeted NGS,corresponding to 44 mutations of which 33 were new. 26(56.5%) patients with results of the assay matching to clinical suspection, including FA (5/11, 45.5%),CSA (6/6,100.0%),CDA (3/8,37.5%) and CHA (12/12,100.0%).2(4.3%)cases not matching to clinical suspection,including dyskeratosis congenital (DC) was made in 1(2.2%) patients with suspected FA and familial hemophagocytic lymphohistiocytosis (FHL) was made in 1(2.2%) patients with suspected unexplained cytopenia (Uc).In 12 CHA patients,the hemolytic type was further clarified by the NGS.The remaining 18 cases were not clearly diagnosed. Conclusion Targeted NGS assay is of major impact on congenital anemias.The assay should be used routinely in congenital anemias.