Kwon Young Dai, Hong Kyung Taek, Lee Juyeon, Sunwoo Yoon, Kim Yeseul, Cho Sung Im, Park Hyun Jin, Kim Bo Kyung, Lee Jee-Soo, Choi Jung Yoon, Seong Moon-Woo, Kang Hyoung Jin
Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
Seoul National University Cancer Research Institute, Seoul, Republic of Korea.
Ann Hematol. 2025 May 13. doi: 10.1007/s00277-025-06392-0.
Inherited bone marrow failure syndromes are genetic hematologic disorders with increased cancer risk. Accurate diagnosis is crucial for appropriate management. This study assessed the clinical usefulness of next-generation sequencing (NGS)-based target gene sequencing in pediatric and AYA (adolescent and young adult) patients with hematologic abnormalities. From December 2019 to June 2023, 93 patients with suspected congenital hematologic diseases at a single institution underwent NGS-based testing. Medical records were retrospectively reviewed. The median age at diagnosis was 9.3 years (range 0.2-31.4), with 59.1% males. Indications for testing included specific medical histories (28 patients), persistent cytopenia or recurrent neutropenic fever (22 patients), changes in cytopenia patterns (11 patients), and other reasons (32 patients). Pathogenic variants were identified in 9/28 (32.1%), 3/22 (13.6%), 4/11 (36.4%), and 0/32 (0%). Overall, 16 patients (17.2%) had pathogenic variants, including FANCA, BRCA2, PMS2, ELANE, G6PC3 and VPS13B in patients with idiopathic neutropenia, and GATA2 in patients with suspected myelodysplastic syndrome. Genetic findings led to diagnostic revisions in 12 patients (12.9%), including reclassification of aplastic anemia (AA) as Fanconi anemia, Diamond-Blackfan anemia, or Shwachman-Diamond syndrome, prompting hematopoietic stem cell transplantation and altering cancer surveillance. Pathogenic variants were more frequently observed in patients with a specific medical history or changes in cytopenia, and in those with additional clinical features (cytogenetic abnormalities or non-severe AA). This study demonstrated the diagnostic usefulness of NGS-based target gene sequencing for pediatric and AYA patients with suspected genetic hematologic disorders, supporting the need for multicenter studies and standardized guideline development.
遗传性骨髓衰竭综合征是一类具有癌症风险增加的遗传性血液系统疾病。准确诊断对于恰当的治疗管理至关重要。本研究评估了基于二代测序（NGS）的靶向基因测序在患有血液学异常的儿科和青少年及青年成人（AYA）患者中的临床实用性。2019年12月至2023年6月，一家机构的93例疑似先天性血液系统疾病患者接受了基于NGS的检测。对病历进行了回顾性审查。诊断时的中位年龄为9.3岁（范围0.2 - 31.4岁），男性占59.1%。检测指征包括特定病史（28例患者）、持续性血细胞减少或复发性中性粒细胞减少性发热（22例患者）、血细胞减少模式改变（11例患者）以及其他原因（32例患者）。在28例中有9例（32.1%）、22例中有3例（13.6%）、11例中有4例（36.4%）以及32例中有0例（0%）检测到致病变异。总体而言，16例患者（17.2%）存在致病变异，包括特发性中性粒细胞减少症患者中的FANCA、BRCA2、PMS2、ELANE、G6PC3和VPS13B，以及疑似骨髓增生异常综合征患者中的GATA2。基因检测结果导致12例患者（12.9%）的诊断被修订，包括将再生障碍性贫血（AA）重新分类为范可尼贫血、先天性纯红细胞再生障碍性贫血或施-戴综合征，促使进行造血干细胞移植并改变癌症监测。致病变异在有特定病史或血细胞减少改变的患者以及有其他临床特征（细胞遗传学异常或非重度AA）的患者中更频繁地被观察到。本研究证明了基于NGS的靶向基因测序对疑似遗传性血液系统疾病的儿科和AYA患者的诊断实用性，支持了开展多中心研究和制定标准化指南的必要性。
