Zhang R R, Chen X J, Ren Y Y, Yang W Y, Zhu X F
Pediatric Blood Disease Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
Zhonghua Xue Ye Xue Za Zhi. 2021 Apr 14;42(4):308-312. doi: 10.3760/cma.j.issn.0253-2727.2021.04.007.
To analyze the clinical features, bone marrow features, and gene mutations of children with familial platelet disorder with predisposition to myeloid leukemia (FPD/AML) caused by a RUNX1 germline mutation as well as their family members. The clinical data and gene mutations of a child with FPD/AML hospitalized in the Pediatric Blood Disease Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and some family members were extracted and analyzed. The literature was searched using "RUNX1 germline mutation" and "FPD/AML" as keywords in the Chinese databases; also PubMed was reviewed until September 2020. A male patient aged 5 with dermatorrhagia was admitted due to thrombocytopenia for more than 3 years. The laboratory tests revealed a peripheral blood routine (WBC 6.38×10(9)/L, HGB 113 g/L, PLT 54×10(9)/L, NEUT 4.03×10(9)/L, and MPV 9.1 fl) . Bone marrow smear revealed dysplasia of megakaryocytes. The immunohistochemistry for CD42b and CD41 highlighted small mononuclear megakaryocytes. Second generation sequencing revealed RUNX1 (exon3:c.520delC: p.R174Efs*10, NM_001001890) frameshift mutations, and its germline mutation was verified via genetic detection of oral epithelial cells. Five members of the family had blood diseases and successively died. The child's mother and maternal grandfather were sequenced for the second generation, and RUNX1 frameshift mutation was detected in the same locus as the child. However, the clinical features among them were different. A total of 37 English literatures were retrieved, and more than 70 FPD/AML families were reported. No relevant Chinese literature was retrieved. Runx1 germline mutations cause FPD/AML with a high risk of progression to myeloid malignancy. Family members carrying the same mutations may exhibit different clinical features and severity.
分析由RUNX1种系突变引起的易患髓系白血病的家族性血小板疾病（FPD/AML）患儿及其家庭成员的临床特征、骨髓特征和基因突变情况。提取并分析了中国医学科学院血液病医院（和平院区）儿童血液病诊疗中心收治的1例FPD/AML患儿及其部分家庭成员的临床资料和基因突变情况。以“RUNX1种系突变”和“FPD/AML”为关键词检索中文数据库，并检索PubMed至2020年9月。1例5岁男性患儿因血小板减少3年余伴皮肤出血入院。实验室检查示外周血常规（白细胞6.38×10⁹/L，血红蛋白113g/L，血小板54×10⁹/L，中性粒细胞4.03×10⁹/L，平均血小板体积9.1fl）。骨髓涂片示巨核细胞发育异常。CD42b和CD41免疫组化显示小单核巨核细胞。二代测序显示RUNX1（外显子3：c.520delC：p.R174Efs*10，NM_001001890）移码突变，通过口腔上皮细胞基因检测验证其种系突变。该家族5名成员患有血液系统疾病并相继死亡。对患儿母亲及外祖父进行二代测序，在与患儿相同位点检测到RUNX1移码突变，但临床特征不同。共检索到37篇英文文献，报道了70多个FPD/AML家系。未检索到相关中文文献。RUNX1种系突变导致FPD/AML，进展为髓系恶性肿瘤的风险较高。携带相同突变的家庭成员可能表现出不同的临床特征和严重程度。
