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目的:分析4例不明原因的溶血性贫血患者的基因变异类型。方法:采集4例以溶血性贫血为表型的患者及其家系成员外周静脉血，提取基因组DNA。应用高通量测序方法对4例患者红系相关疾病基因进行筛查，并用Sanger测序验证患者及其家系成员可疑变异位点。结果:4个先证者在n SEC23B基因上均检测到2个复合杂合变异，分别来自其父母，为先天性红细胞生成异常性贫血(congenital dyserythropoietic anemia，CDA)Ⅱ型患者。先证者1携带n SEC23B基因第15外显子c.1727T>C(p.Phe576Ser)和第16外显子c.1831C>T(p.Arg611Trp)复合杂合变异；先证者2携带第2外显子c.74C>A(p.Pro25His)和第14外显子c.1588C>T(p.Arg530Trp)复合杂合变异；先证者3携带第2外显子c.74C>A(p.Pro25His)和第16外显子c.1831C>T(p.Arg611Trp)复合杂合变异；先证者4及其弟携带第14外显子c.1571C>T (p.Ala524Val)和第19外显子c.2149G>T (p.Ala717Ser)复合杂合变异；检出的6个变异中，c.1727T>C(p.Phe576Ser)和c.2149G>T (p.Ala717Ser)为未见报道过的新变异。同时检测到先证者4其n PIEZO1基因上存在c.4608_4615del(p.Gly1537Glufs*82)杂合变异。n 结论:高通量测序技术可快速准确地对CDAⅡ型患者进行基因变异分析，是传统诊断方法的有效补充手段，其中新发现的变异位点丰富了n SEC23B基因的变异数据库。n “,”Objective:To identify the pathogenic variants of 4 patients with hemolytic anemia of unknown cause.Methods:Peripheral blood samples of the patients and their family members were collected to extract DNA. The coding region and splice region in all exons of gene of erythrocyte related diseases were analyzed by using target sequence capture and high-throughput sequencing technology. Suspected pathogenic variants were verified by PCR combined Sanger sequencing technology.Results:Each of the probands was detected two compound heterozygous variants, and CDA II was diagnosed. Six variants were detected in the 4 probands, four variants were reported and the other two were first reported.Conclusion:By high-throughput sequencing, gene variant of CDA Ⅱ be analyzed fast and accurately. It is an effective supplement to convenional diagnostic methods. Furthermore, the novel variant sites have enriched the variant database of the n SEC23B gene.n