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.
Key words
Cytopenia /
Malformation /
Fanconi anemia /
LIG4 syndrome /
Child
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
1 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.
2 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.
3 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.
4 Chrzanowska KH, Gregorek H, Dembowska-Bagińska B, et al. Nijmegen breakage syndrome (NBS)[J]. Orphanet J Rare Dis, 2012, 7: 13. PMID: 22373003. PMCID: PMC3314554. DOI: 10.1186/1750-1172-7-13.
5 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.
6 Taylor AMR, Rothblum-Oviatt C, Ellis NA, et al. Chromosome instability syndromes[J]. Nat Rev Dis Primers, 2019, 5(1): 64. PMID: 31537806. PMCID: PMC10617425. DOI: 10.1038/s41572-019-0113-0.
7 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.
8 Park J, Welner RS, Chan MY, et al. The DNA ligase IV syndrome R278H mutation impairs B lymphopoiesis via error-prone nonhomologous end-joining[J]. J Immunol, 2016, 196(1): 244-255. PMID: 26608917. PMCID: PMC4684978. DOI: 10.4049/jimmunol.1403099.
9 Peake JD, Noguchi E. Fanconi anemia: current insights regarding epidemiology, cancer, and DNA repair[J]. Hum Genet, 2022, 141(12): 1811-1836. PMID: 35596788. DOI: 10.1007/s00439-022-02462-9.
10 Sun B, Chen Q, Wang Y, et al. LIG4 syndrome: clinical and molecular characterization in a Chinese cohort[J]. Orphanet J Rare Dis, 2020, 15(1): 131. PMID: 32471509. PMCID: PMC7257218. DOI: 10.1186/s13023-020-01411-x.
11 张潇潇, 陆敏, 顾浩翔, 等. 一例因基因突变致LIG4综合征病例的临床特点及分析[J]. 基础医学与临床, 2020, 40(6): 825-830. DOI: 10.3969/j.issn.1001-6325.2020.06.017.
12 Altmann T, Gennery AR. DNA ligase IV syndrome; a review[J]. Orphanet J Rare Dis, 2016, 11(1): 137. PMID: 27717373. PMCID: PMC5055698. DOI: 10.1186/s13023-016-0520-1.
PDF(559 KB)
