Two cases of cytopenia associated with multiple malformations
CHANG Li-Xian, ZHANG Li, GAO Yi-Man, ZHU Xiao-Fan
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College/State Key Laboratory of Experimental Hematology/National Clinical Research Center for Blood Diseases/Haihe Laboratory of Cell Ecosystem, Tianjin 300020, China (Email: changlixian@ihcams.ac.cn)
摘要 患儿1，女，10岁，因全血细胞减少伴反复鼻衄就诊，有反复上呼吸道感染史，有皮肤咖啡斑、小头畸形，基因检测发现DNA连接酶IV（ligase IV, LIG4）基因存在复合杂合变异，诊断为LIG4综合征。患儿2，女，6岁，因血小板减少2年余就诊，有身材矮小、皮肤黝黑、手部畸形等，染色体断裂试验检查结果为阳性，诊断为范可尼贫血互补组A型。该2例患儿临床表现相似，最终诊断为两类疾病，提示血细胞减少伴畸形的患儿并非仅是血液病，需警惕免疫系统等其他疾病。
Abstract：The first patient, a 10-year-old girl, presented with pancytopenia and recurrent epistaxis, along with a history of repeated upper respiratory infections, café-au-lait spots, and microcephaly. Genetic testing revealed compound heterozygous mutations in the DNA ligase IV (LIG4) gene, leading to a diagnosis of LIG4 syndrome. The second patient, a 6-year-old girl, was seen for persistent thrombocytopenia lasting over two years and was noted to have short stature, hyperpigmented skin, and hand malformations. She had a positive result from chromosome breakage test. She was diagnosed with Fanconi anemia complementation group A. Despite similar clinical presentations, the two children were diagnosed with different disorders, suggesting that children with hemocytopenia and malformations should not only be evaluated for hematological diseases but also be screened for other potential underlying conditions such as immune system disorders.
O'Driscoll M, Cerosaletti KM, Girard PM, et al. DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency[J]. Mol Cell, 2001, 8(6): 1175-1185. PMID: 11779494. DOI: 10.1016/s1097-2765(01)00408-7.
Buck D, Moshous D, de Chasseval R, et al. Severe combined immunodeficiency and microcephaly in siblings with hypomorphic mutations in DNA ligase IV[J]. Eur J Immunol, 2006, 36(1): 224-235. PMID: 16358361. DOI: 10.1002/eji.200535401.
Levran O, Diotti R, Pujara K, et al. Spectrum of sequence variations in the FANCA gene: an International Fanconi Anemia Registry (IFAR) study[J]. Hum Mutat. 2005, 25(2): 142-149. PMID: 15643609. DOI: 10.1002/humu.20125.
O'Driscoll M, Ruiz-Perez VL, Woods CG, et al. A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome[J]. Nat Genet, 2003, 33(4): 497-501. PMID: 12640452. DOI: 10.1038/ng1129.
McKay MJ, Craig J, Kalitsis P, et al. A Roberts syndrome individual with differential genotoxin sensitivity and a DNA damage response defect[J]. Int J Radiat Oncol Biol Phys, 2019, 103(5): 1194-1202. PMID: 30508616. DOI: 10.1016/j.ijrobp.2018.11.047.
