Department of Hematology and Oncology, Beijing Children's Hospital, Capital Medical University, Nanlishi Road No. 56, Xicheng District, Beijing, 100045, People's Republic of China.
Hematology and Oncology Laboratory, Beijing Pediatric Research Institute, National Center for Children's Health, Beijing Key Laboratory of Pediatric Hematology Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics, Beijing Children's Hospital Affiliated to Capital Medical University, Beijing, 100045, China.
Ann Hematol. 2019 Oct;98(10):2303-2310. doi: 10.1007/s00277-019-03764-1. Epub 2019 Aug 6.
To study the genetic characteristics of primary hemophagocytic lymphohistiocytosis (pHLH) in China, we investigated the genetic data and clinical features of Chinese HLH patients. We retrospectively reviewed the genetic and clinical data of patients with HLH from November 2015 to June 2018. As a result, 26 patients were diagnosed with pHLH. The median age at diagnosis was 2.8 years (range 0.1-13.7 years). The probable overall survival at 12 and 24 months was 87.6% and 62.6%, respectively. Mutations in PRF1 (38.4%) and UNC13D (26.9%) were the most common genetic abnormalities. Furthermore, we identified 19 novel mutations that had not been previously reported and were predicted to likely be pathogenic. In addition to HLH-associated genes, there were 27 other genes identified. Genotype-phenotype analysis showed that patients with disruptive mutations were significantly younger at diagnosis than those with other mutation types (2.9 years vs. 6.4 years, P = 0.036). Familial HLH patients were more prone to central nervous system involvement and seizures compared with other patients (83.3% vs. 37.5%, P = 0.019; 55.6% vs. 12.5%, P = 0.04, respectively). In summary, numerous new mutations in HLH-related genes and other genes were identified in Chinese children with pHLH. Significantly, disruptive mutation types were more likely to be found in younger patients, and familial HLH patients tended to exhibit central nervous system involvement and seizures.
为了研究中国原发性噬血细胞性淋巴组织细胞增多症（pHLH）的遗传特征，我们调查了中国 HLH 患者的遗传数据和临床特征。我们回顾性分析了 2015 年 11 月至 2018 年 6 月期间 HLH 患者的遗传和临床数据。结果，26 例患者被诊断为 pHLH。诊断时的中位年龄为 2.8 岁（范围 0.1-13.7 岁）。12 个月和 24 个月的总生存率分别为 87.6%和 62.6%。PRF1（38.4%）和 UNC13D（26.9%）的突变是最常见的遗传异常。此外，我们还发现了 19 种以前未报道过且预测可能为致病性的新突变。除了 HLH 相关基因外，还鉴定出了 27 个其他基因。基因型-表型分析表明，具有破坏性突变的患者的诊断年龄明显小于其他突变类型（2.9 岁 vs. 6.4 岁，P=0.036）。家族性 HLH 患者比其他患者更容易发生中枢神经系统受累和癫痫发作（83.3% vs. 37.5%，P=0.019；55.6% vs. 12.5%，P=0.04）。总之，在中国患有 pHLH 的儿童中发现了许多新的 HLH 相关基因和其他基因的突变。重要的是，破坏性突变类型更可能出现在年轻患者中，而家族性 HLH 患者往往表现出中枢神经系统受累和癫痫发作。
