PDF(Pubmed)
Abstract：
Hereditary hemolytic anemia (HHA) refers to a heterogeneous group of genetic disorders that share one common feature: destruction of circulating red blood cells (RBCs). The destruction of RBCs may be due to membranopathies, enzymopathies, or hemoglobinopathies. Because these are genetic disorders, incorporation of next-generation sequencing (NGS) has facilitated the diagnostic process of HHA.
Genetic data from 29 patients with suspected hereditary anemia in a tertiary hospital were retrospectively reviewed to evaluate the efficacy of NGS on hereditary anemia diagnosis. Targeted NGS was performed with custom probes for 497 genes associated with hematologic disorders. After genomic DNA was extracted from peripheral blood, prepared libraries were hybridized with capture probes and sequenced using NextSeq 550Dx (Illumina, San Diego, CA, USA).
Among the 29 patients, ANK1 variants were detected in five, four of which were pathogenic or likely pathogenic variants. SPTB variants were detected in six patients, five of which were classified as pathogenic or likely pathogenic variants. We detected g6pd pathogenic and spta1 likely pathogenic variants in two patients and one patient, respectively. Whole-gene deletions in both HBA1 and HBA2 were detected in two patients, while only HBA2 deletion was detected in one patient. One likely pathogenic variant in PLKR was detected in one patient, and one likely pathogenic variant in ALAS2 was detected in another.
Here, NGS played a critical role in definitive diagnosis in 18 out of 29 patients (62.07%) with suspected HHA. Thus, its incorporation into the diagnostic workflow is crucial.
Genetic data from 29 patients with suspected hereditary anemia in a tertiary hospital were retrospectively reviewed to evaluate the efficacy of NGS on hereditary anemia diagnosis. Targeted NGS was performed with custom probes for 497 genes associated with hematologic disorders. After genomic DNA was extracted from peripheral blood, prepared libraries were hybridized with capture probes and sequenced using NextSeq 550Dx (Illumina, San Diego, CA, USA).
Among the 29 patients, ANK1 variants were detected in five, four of which were pathogenic or likely pathogenic variants. SPTB variants were detected in six patients, five of which were classified as pathogenic or likely pathogenic variants. We detected g6pd pathogenic and spta1 likely pathogenic variants in two patients and one patient, respectively. Whole-gene deletions in both HBA1 and HBA2 were detected in two patients, while only HBA2 deletion was detected in one patient. One likely pathogenic variant in PLKR was detected in one patient, and one likely pathogenic variant in ALAS2 was detected in another.
Here, NGS played a critical role in definitive diagnosis in 18 out of 29 patients (62.07%) with suspected HHA. Thus, its incorporation into the diagnostic workflow is crucial.
摘要：
背景：遗传性溶血性贫血（HHA）是指一组具有一个共同特征的异质性遗传疾病：循环红细胞（RBC）的破坏。红细胞的破坏可能是由于膜病，酶病，或者血红蛋白病。因为这些是遗传性疾病，下一代测序（NGS）的掺入促进了HHA的诊断过程。
方法：回顾性分析了三甲医院29例疑似遗传性贫血患者的遗传数据，以评估NGS对遗传性贫血诊断的疗效。用与血液疾病相关的497个基因的定制探针进行靶向NGS。从外周血中提取基因组DNA后，将制备的文库与捕获探针杂交，并使用NextSeq550Dx（Illumina，圣地亚哥,CA,美国）。
结果：在29例患者中，ANK1变异体检测到五个，其中四种是致病性或可能的致病性变异。在6例患者中检测到SPTB变异，其中5种被分类为致病性或可能的致病性变异。我们在两名患者和一名患者中检测到g6pd致病性和spta1可能的致病性变异，分别。在两名患者中检测到HBA1和HBA2的全基因缺失，而在一名患者中仅检测到HBA2缺失。在一名患者中检测到PLKR的一个可能的致病变异，并且在ALAS2中检测到一个可能的致病变异。
结论：这里，NGS在29例疑似HHA患者中的18例（62.07％）的明确诊断中起着至关重要的作用。因此，将其纳入诊断工作流程至关重要。
方法：回顾性分析了三甲医院29例疑似遗传性贫血患者的遗传数据，以评估NGS对遗传性贫血诊断的疗效。用与血液疾病相关的497个基因的定制探针进行靶向NGS。从外周血中提取基因组DNA后，将制备的文库与捕获探针杂交，并使用NextSeq550Dx（Illumina，圣地亚哥,CA,美国）。
结果：在29例患者中，ANK1变异体检测到五个，其中四种是致病性或可能的致病性变异。在6例患者中检测到SPTB变异，其中5种被分类为致病性或可能的致病性变异。我们在两名患者和一名患者中检测到g6pd致病性和spta1可能的致病性变异，分别。在两名患者中检测到HBA1和HBA2的全基因缺失，而在一名患者中仅检测到HBA2缺失。在一名患者中检测到PLKR的一个可能的致病变异，并且在ALAS2中检测到一个可能的致病变异。
结论：这里，NGS在29例疑似HHA患者中的18例（62.07％）的明确诊断中起着至关重要的作用。因此，将其纳入诊断工作流程至关重要。
