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WAS基因突变与临床表型的相关性分析

Analysis of Correlation of WAS Gene Mutations with Clinical Phenotype
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摘要 目的:探讨WAS基因缺陷患者的基因突变及其与临床表型的相关性。方法:回顾性分析苏州大学附属儿童医院血液科2013年1月-2018年2月发现WAS基因突变的31例病人突变热点与临床表型的关系。结果:患儿均为男性,发病中位年龄1(0-83)个月,突变体共检出25种,其中新发突变9种,包括c.12341235dupCC,c.1093-1097delG,c.28-30dupC,c.436G>T,c.273+10273+11dupCC,c.995996insG,c.1010T>A,c.332333delCC,c.683C> T。临床表型包括经典WAS 25例,其突变类型包括错义突变、剪接体突变、插入突变、缺失突变、无义突变;X连锁的血小板减少症(XLT)2例均由错义突变引起;1例间歇性X连锁的血小板减少症(IXLT)由剪接体突变引起;X连锁的全血细胞减少症(XLP)共2例,是由错义突变引起。对IXLT患者丙种球蛋白及激素治疗有效,且能持续缓解;对XLT患者丙种球蛋白、激素治疗血小板一过性有效;对经典WAS患者丙种球蛋白或激素治疗仅少部分患者血小板一过性有效(8.0%);对XLP患者丙种球蛋白、激素治疗血小板低下状态无改善。免疫学检测发现CD3+降低患者占60.0%,CD19+降低患者占12.0%,CD56+CD16+降低患者占16.0%。本研究中24例接受造血干细胞移植(HSCT),存活22例,放弃HSCT的病人5例,4例死亡,只有1例IXLT的病人存活。结论:WAS基因缺陷是WAS及相关疾病确诊的重要依据。少数病人采用丙种球蛋白+激素治疗一过性有效,需要鉴别诊断。HSCT是治疗WAS的最有效手段。 Objective: To investigate the gene mutation of patients with WAS gene defect and its correlation with clinical manifestations. Methods: Thirty-one patients consulted in Children’s Hospital of Soochow University from January 2013 to February 2018 were enrolled in this study. The hot pot mutations of WAS gene in 31 patients were detected and related clinical phenotypes were analyzed retrospectively. Results: All patients were male. The median onset age was 1 month(range, 0-83 months). Nine mutants were reported as novel mutations among 25 mutants detected in 31 patients, including c.12341235dupCC, c.1093-1097 delG, c.28-30 dupC, c.436G>T, c.273 + 10273 + 11 dupCC, c.995996insG, c.1010 T >A, c.332333delCC and c.683 C >T mutations. There were 25 cases of classic WAS which mutations included missense mutation, deletion mutation, insertion mutation, splicing mutation and nonsense mutation, 2 cases of X-linked thrombocytopenia(XLT) were induced by missense mutation, 1 case of intermittent X-linked thrombocytopenia(IXLT) was induced by splicing mutation, 2 cases of X-linked pancytopenia were induced by missense mutation. Intravenous immunoglobulin(IVIG) and glucocorticoid therapy in IXLT patient was effective, and remission could be sustained, platelets could be increased in the short-term in treated XLT patients, but only a small part of classic WAS patients(8.0%) showed transient response to it, the IVIG and glucocorticoid therapy did not improve the status of platelet in XLP patients. Immune laboratory examination showed that CD3+ was decreased in 60.0% patients, CD19+ was decreased in 12.0% patients, and CD56+CD16+ in 4 patients was decreased, accounting for 16.0%. Out of 24 patients, 22 patients were alive after treated with hematopoietic stem cell transplantation(HSCT), 4 patients who were not given HSCT died of brain bleeding and severe infection, 1 patient diagnosed as IXLT got remission and survived. Conclusion: WAS gene defect is an important basis for the diagnosis of WAS and related diseases. IVIG plus gluc
作者 郑云菁 陆芹 姚艳华 何海龙 李建琴 肖佩芳 胡绍燕 ZHENG Yun-Jing;LU Qin;YAO Yan-Hua;HE Hai-Long;LI Jian-Qin;XIAO Pei-Fang;HU Shao-Yan(Deparonent of Hematology,The Affiliated Children's Hospital of Soochow University,Suzhou 215000,Jiangsu Province,China)
出处 《中国实验血液学杂志》 CAS CSCD 北大核心 2019年第1期246-252,共7页 Journal of Experimental Hematology
基金 苏州市临床重点病种诊疗技术专项项目(LCZX201507) 苏州市临床医学中心项目(SZZX201504) 苏州市儿童白血病重点实验室(SZS201615) 江苏省医学创新团队项目(CXTDA2017014) 苏州市民生科技项目(SYS201643).
关键词 WISKOTT-ALDRICH综合征 WAS基因突变 造血干细胞移植 Wiskott-Aldrich syndrome WAS gene mutation hematopoietic stem cell transplantation
作者简介 通讯作者:胡绍燕,主任医师,教授,博士生导师,E-mail:hsy139@126.com.
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