摘要目的 分析具有明确致病基因突变的先天性纯红细胞再生障碍性贫血(Diamond-Blackfan anemia,DBA)患儿基因突变与临床表型及治疗反应的相关性.方法 回顾分析DBA中国及首都医科大学附属北京儿童医院2009年12月至2017年10月诊治及随访的42例具有明确致病基因突变的DBA患儿的临床资料及基因检测结果,统计分析其相关性.结果 42例患儿中位随访40个月(1～ 136个月),尚无成功停药患儿.检测到RPL5、RPL11、RPL35a、RPS17、RPS19、RPS24和RPS26共7种突变,最常见的基因突变是RPS19(42.9％),其次是RPL11(19.0％)、RPS17(11.9％)、RPS26(11.9％)、RPLS(7.1％)和RPL35a(4.8％).发病时血红蛋白中位水平为42.5 g/L,12例患儿存在身体畸形,以心脏畸形及手指畸形最为常见.37例患儿接受激素治疗,初期总反应率为89.2％(33/37例),激素无效患儿中1例使用环孢素(CSA)治疗有效,其余3例予输血治疗.结论 DBA患儿基因突变以RPS19最为常见,RPS17突变以拷贝数变异为主,在进行DBA基因检测时需注意大片段缺失可能.RPL5突变患儿畸形发生率高,各组患儿在发病年龄、发病时血红蛋白水平、畸形发生率及激素治疗有效率方面差异无统计学意义.

abstractsObjective To analyze the correlation between genotype,clinical manifestations and treatment response in patients diagnosed as Diamond-Blackfan anemia (DBA) with a clear pathogenic gene mutation.Methods Retrospective investigation was performed of the genetic and clinical data of 42 patients diagnosed as DBA with a definite mutation from December 2009 to October 2017 in Beijing Children's Hospital,Capital Medical University and DBA China group.Results Among 42 patients,no one patient could successfully stop the therapy during the median follow-up time of 40 months (1-136 months).Nucleotide-level mutations or large deletions were identified in 7 ribosomal genes as RPL5,RPL11,RPL35a,RPS17,RPS19,RPS24 and RPS26.The most common gene mutation group was RPS19 (42.9％),followed by RPL11(19.0％),RPS17(11.9％),RPS26(11.9％),RPL5 (7.1％) and RPL35a(4.8％).The median onset hemoglobin level was 42.5 g/L.A total of 12 patients had physical malformation,with the most common on heart and fingers.A total of 37 patients received hormone therapy,and the total initial response rate was 89.2％ (33/37 cases).One of the patients with hormone inefficiency was treated successfully with cyclosporin A,and the other 3 patients were treated with blood transfusion.Conclusions RPS19 was the most common gene mutation in DBApatients.Most of the RPS17 mutations were copy number variation.The deletion of large fragments should be paid more attention to in the detection of DBA genetic analysis.Patients with RPL5 mutation showed more malformation than other groups.No significant difference was found in terms of age of onset,hemoglobin level of onset,incidence of malformation and effective rate of hormone treatment in each group.