TRNT1基因突变致SIFD 2例临床特征分析及文献复习.pdf

Med J Chin PLA,Vol.48,No.7,July 28,2023823TRNT1基因突变致SIFD 2例临床特征分析及文献复习陈香元1，符芳2，莫小兰3，李茹2，张松1，程苏云1，曾华松1*1广州医科大学附属妇女儿童医疗中心过敏免疫风湿科/广东省儿童健康与疾病临床医学研究中心，广东广州510623；2广州医科大学附属妇女儿童医疗中心优生围产研究所/广东省儿童健康与疾病临床医学研究中心，广东广州510623；3广州医科大学附属妇女儿童医疗中心药学部/广东省儿童健康与疾病临床医学研究中心，广东广州510623临床研究基金项目广州市卫生健康科技一般引导项目(20211A011024)作者简介陈香元，医学硕士，主治医师，主要从事免疫性疾病及风湿性疾病方面的研究通信作者曾华松，E-mail：论著中图分类号R725.9文献标志码ADOI10.11855/j.issn.0577-7402.0845.2022.1229声明本文所有作者声明无利益冲突引用本文陈香元,符芳,莫小兰,等.TRNT1基因突变致SIFD 2例临床特征分析及文献复习J.解放军医学杂志,2023,48(7):823-827.收稿日期2022-04-18录用日期2022-10-06上线日期2022-12-29摘要目的分析2例父母无亲缘关系的同胞TRNT1基因突变致铁粒幼细胞贫血、B细胞免疫缺陷、周期性发热和发育迟缓(SIFD)的临床特征及基因表型，为临床医师对SIFD的认识提供参考。方法收集广州市妇女儿童医疗中心过敏免疫风湿科确诊的2例姐弟SIFD患儿的临床资料，抽取患儿及其父母外周血进行全基因组测序分析。检索PubMed、中国知网及万方数据库，总结55例患者的临床特征及基因分析结果。结果先证者，女，15岁，自生后8个月起出现反复发热、炎性标志物升高；1岁以后渐出现右膝关节肿痛继发屈曲畸形、双眼白内障并失明，发育迟缓，生长停滞，至今不会说话，不能行走，无月经来潮。先证者同胞弟弟，男，7岁，生后3个月左右体检发现低免疫球蛋白血症，B细胞计数正常；4个月起出现腹泻，8个月左右因发热、支气管肺炎、腹泻住院，此后易反复发热、腹泻；生后19个月时出现双膝关节炎，2岁出现双眼白内障，复查免疫球蛋白A低于正常，B淋巴细胞计数正常，自27个月起不定期输注免疫球蛋白，关节肿痛渐有好转，发热次数减少；发育迟缓，生长停滞，能说简单的37字的短句，发音欠清晰，能理解并执行父母的命令；能独走，稳定性欠佳。对患儿及其父母外周血进行全基因组测序发现，两例患儿均携带TNRT1基因c.1056+1GA及c.1246AG(p.K416E)复合杂合突变。文献共报道病例55例，男21例，女30例，另4例文献中未提及性别；临床表现为反复发热、不同程度的铁粒幼细胞贫血和免疫学异常、关节炎、发育迟缓、听力异常、白内障、反复感染、皮疹等；静脉输注免疫球蛋白、肿瘤坏死因子-拮抗剂、造血干细胞移植及积极的对症处理可改善预后。结论TRNT1基因突变致SIFD为常染色体隐性遗传性疾病，其临床表现多样；临床诊断依据为基因检测，明确TRNT1基因致病性突变；临床医师应提高对该病的认识，早期诊断及干预治疗可提高患儿的生活质量。关键词SIFD；基因，TRNT1；免疫缺陷综合征；白内障；发育障碍Clinical characteristics and literature review of 2 cases of SIFD due to TRNT1 mutationChen Xiang-Yuan1,Fu Fang2,Mo Xiao-Lan3,Li Ru2,Zhang Song1,Cheng Su-Yun1,Zeng Hua-Song1*1Department of Allergy,Immunology and Rheumatology,2Institute of Birth Health and Perinatal Medicine,3Department of Pharmacy,Guangzhou Women and Childrens Medical Center,Guangzhou Medical University/Guangdong Provincial Clinical Research Center for Child Health,Guangzhou,Guangdong 510623,China*Corresponding author,E-mail:This work was supported by the General Guidance Project of Guangzhou Health Science and Technology(20211A011024)AbstractObjectiveTo analyze the clinical features and gene phenotype of sideroblastic anemia,B-cell immunodeficiency,periodic fevers,and developmental delay(SIFD)due to TRNT1 mutation in two siblings from non-consanguineous parents.MethodsThe clinical data of the siblings with SIFD that were diagnosed in the department of allergy,immunology and rheumatology of Guangzhou Women and Childrens Medical Center were collected.Then we detected the whole genome sequencing analysis with the peripheral blood samples of the patients and their parent.We summarize the clinical 解放军医学杂志2023年7月28日第48卷第7期824characteristics and gene analysis of 55 patients with SIFD that were concluded from the PubMed,China national knowledge internet and Wanfang databases.ResultsThe proband was a 15-year-old girl,she presented with recurrent fever and elevated inflammatory markers since she was 8 months of age.After 1 year-old of age,she gradually developed swelling and arthralgia of the right knee,flexion deformity of arthritis,bilateral cataract,developmental delay and growth retardation.She cant talk with others,cant walk by herself and had no menstruation until now.The probands sibling brother was 7 years old,presented with hypoimmunoglobulinemia and normal B cell counts at 3 months,which showed low immunoglobulin A but with normal immunoglobulin G and M and normal B cell counts at 2 years old.Diarrhea appeared at 4 months of age.He was hospitalized with fever,bronchopneumonia and diarrhea at 8 months of age.Since then,he was prone to recurrent fever and diarrhea.At 19 months,he developed arthritis of both knees and presented bilateral cataract at the age of 2 years.Irregular infusion of immunoglobulin was performed,swelling and pain of the knee gradually improved and the frequency of fever decreased.Now,he still presents with developmental delay and growth retardation.He can talk with people by 3-7 words short sentences,but the pronunciation is not clear.He can understand and carry out the orders of his parent.He can walk alone but with poor stability.Whole genome sequencing of the blood revealed biallelic TRNT1 heterozygous mutations,c.1056+1GA/c.1246AG(p.K416E).A total of 55 cases were reported in the literatures,including 21 males and 30 females,and 4 cases were not mentioned in the references.The clinical manifestations presented with repeated fever,different levels of sideroblastic anemia and immunologic abnormalities,arthritis,growth retardation,hearing abnormalities,cataracts,repeated infections,skin rashes and so on.Intravenous infusion of immunoglobulin and tumor necrosis factor-antagonists,hematopoietic stem cell transplantation and positive symptomatic treatments may improve the prognosis.ConclusionsSIFD caused by TRNT1 gene mutation is an autosomal recessive inherited disease with diverse clinical manifestations.Genetic testing of TRNT1 gene mutationis is the basis of clinical diagnosis.Clinicians should recognize the complex disease,early diagnosis and intervention can improve the