Abstract: Objective    To explore the clinical and genetic characteristics of LIG4 syndrome. Methods    We retrospectively analyzed the clinical data of 3 patients with LIG4 syndrome who were admitted to ShangHai Children’S Hospital from Jun 2014 to Aug 2018，and reviewed related articles. Results    All 3 cases were female，presented with recurrent chronic diarrhea or recurrent respiratory infections.The clinical manifestations were microcephaly，a special“bird-head-like”face，growth retardation，and repeated infections.The blood routine showed that the lymphocyte count was significantly reduced，the immune function showed that the counts of T and B lymphocytes were decreased，and immunodeficiency disease was considered clinically. The gene detection revealed that P1 had homozygous mutation of LIG4 gene，c.833G>T（p.R278L），with severe clinical phenotype；P2 had LIG4 gene complex heterozygous mutations，c.883G>T（p.R278L）and c.1144-1145delCT（p.L382EfsX5）；P3 had LIG4 gene complex heterozygous mutations，c.28-29delGT（p.vall0fs）and c.1341G>T（p.Trp447cys），where the frameshift gene mutation site，c.28-29delGT（p.vall0fs），had not been reported.P1 died of severe infection and multiple organ dysfunction syndrome. P2 had preventive anti-infection treatment and received regular human immunoglobulin infusion，who still had recurrent infection and lost follow-up.P3 underwent peripheral blood hematopoietic stem cell transplantation，and established normal immune function.She did not have recurrent infection during 2-year follow-up period. A total of 46 cases of LIG4 syndrome had been published worldwide，including 13 cases and 1 family report of LIG4 syndrome in China. Conclusion    Immunodeficiency diseases should be considered in the patients with chronic multiple infections accompanied by T and B lymphocytes decrease，growth retardation，and microcephaly.Gene testing helps confirm the diagnosis and prenatal screening.Hematopoietic stem cell transplantation is effective for immune reconstitution.

Key words: DNA ligase Ⅳ syndrome, immunodeficiency, infection, hematopoietic stem cell transplantation

摘要： 目的    探讨LIG4综合征的临床及基因特征。方法    回顾性分析上海交通大学医学院附属儿童医院消化感染科2014年6月至2018年9月收治的3例LIG4综合征患儿的临床资料，并复习相关文献。结果    3例患儿均为女性，均以反复慢性腹泻或反复呼吸道感染就诊，临床表现为小头畸形，“鸟头样”特殊面容，生长发育迟缓及反复感染等典型表现；血常规示淋巴细胞绝对值明显降低，免疫功能示T、B淋巴细胞计数减少，临床倾向于免疫缺陷病。基因检测结果示例1存在LIG4致病基因纯合变异，c.833G>T（p.R278L），具有严重临床表型；例2存在LIG4致病基因复合杂合变异，c.883G>T（p.R278L）、c.1144_1145delCT（p.L382EfsX5）；例3存在LIG4致病基因复合杂合变异，c.28_29delGT（p.vall0fs）、c.1341G>T（p.Trp447cys），其中此移码突变位点c.28_29delGT尚未见报道。例1因严重感染、多器官功能衰竭（MODS）死亡；例2行预防性抗感染，定期输注人免疫球蛋白支持，仍有反复感染，后失访；例3行亲缘外周血造血干细胞移植治疗，重建正常免疫功能，现随访近2年未发生反复感染。检索到国内外文献已发表的LIG4综合征共有46例报道，其中国内报道13例和1个LIG4综合征家系。结论    临床上表现为反复多重感染且伴有T、B淋巴细胞减少、生长发育迟缓、小头畸形的患儿应考虑免疫缺陷病，基因检测有助于诊断及产前筛查。造血干细胞移植对免疫重建有效。

关键词: LIG4综合征, 免疫缺陷, 感染, 造血干细胞移植