|国家科技期刊平台
首页|期刊导航|中国实用儿科杂志|基因突变致LIG4综合征临床及基因特征

基因突变致LIG4综合征临床及基因特征OA北大核心CSTPCD

LIG4 syndrome caused by gene mutation:the clinical and genetic characteristics

中文摘要英文摘要

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.

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.

刘红红;王怡仲;肖咏梅;吴胜男;张育才;张婷

上海交通大学医学院附属儿童医院消化感染科,上海 200062||上海交通大学医学院附属儿童医院重症医学科,上海 200062上海交通大学医学院附属儿童医院消化感染科,上海 200062上海交通大学医学院附属儿童医院分子实验室,上海 200062上海交通大学医学院附属儿童医院重症医学科,上海 200062

临床医学

LIG4综合征免疫缺陷感染造血干细胞移植

DNA ligase Ⅳ syndromeimmunodeficiencyinfectionhematopoietic stem cell transplantation

《中国实用儿科杂志》 2024 (007)

530-538 / 9

国家自然科学基金项目(81870373)

10.19538/j.ek2024070611

评论