Abstract：
BACKGROUND: Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow failure syndrome characterized by erythroid aplasia, physical malformation, and cancer predisposition. Twenty ribosomal protein genes and three non-ribosomal protein genes have been identified associated with DBA.
METHODS: To investigate the presence of novel mutations and gain a deeper understanding of the molecular mechanisms of disease, targeted next-generation sequencing was performed in 12 patients with clinically suspected DBA. Literatures were retrieved with complete clinical information published in English by November 2022. The clinical features, treatment, and RPS10/RPS26 mutations were analyzed.
RESULTS: Among the 12 patients, 11 mutations were identified and 5 of them were novel (RPS19, p.W52S; RPS10, p.P106Qfs*11; RPS26, p.R28*; RPL5, p.R35*; RPL11, p.T44Lfs*40). Including 2 patients in this study, 13 patients with RPS10 mutations and 38 patients with RPS26 mutations were reported from 4 and 6 countries, respectively. The incidences of physical malformation in patients with RPS10 and RPS26 mutations (22% and 36%, respectively) were lower than the overall incidence in DBA patients (~50%). Patients with RPS26 mutations had a worse response rate of steroid therapy than RPS10 (47% vs. 87.5%), but preferred RBC transfusions (67% vs. 44%, p = 0.0253).
CONCLUSIONS: Our findings add to the DBA pathogenic variant database and demonstrate the clinical presentations of the DBA patients with RPS10/RPS26 mutations. It shows that next-generation sequencing is a powerful tool for the diagnosis of genetic diseases such as DBA.
METHODS: To investigate the presence of novel mutations and gain a deeper understanding of the molecular mechanisms of disease, targeted next-generation sequencing was performed in 12 patients with clinically suspected DBA. Literatures were retrieved with complete clinical information published in English by November 2022. The clinical features, treatment, and RPS10/RPS26 mutations were analyzed.
RESULTS: Among the 12 patients, 11 mutations were identified and 5 of them were novel (RPS19, p.W52S; RPS10, p.P106Qfs*11; RPS26, p.R28*; RPL5, p.R35*; RPL11, p.T44Lfs*40). Including 2 patients in this study, 13 patients with RPS10 mutations and 38 patients with RPS26 mutations were reported from 4 and 6 countries, respectively. The incidences of physical malformation in patients with RPS10 and RPS26 mutations (22% and 36%, respectively) were lower than the overall incidence in DBA patients (~50%). Patients with RPS26 mutations had a worse response rate of steroid therapy than RPS10 (47% vs. 87.5%), but preferred RBC transfusions (67% vs. 44%, p = 0.0253).
CONCLUSIONS: Our findings add to the DBA pathogenic variant database and demonstrate the clinical presentations of the DBA patients with RPS10/RPS26 mutations. It shows that next-generation sequencing is a powerful tool for the diagnosis of genetic diseases such as DBA.
摘要：
背景：Diamond-Blackfan贫血（DBA）是一种罕见的先天性骨髓衰竭综合征，以红系发育不全为特征，身体畸形,和癌症倾向。已鉴定出20个核糖体蛋白基因和3个非核糖体蛋白基因与DBA相关。
方法：为了研究新突变的存在，并更深入地了解疾病的分子机制，对12例临床怀疑为DBA的患者进行了靶向下一代测序.到2022年11月，检索到完整的英文临床信息。临床特征，治疗,分析RPS10/RPS26突变。
结果：在12例患者中，鉴定出11个突变,其中5个是新的(RPS19,p.W52S;RPS10,p.P106Qfs*11;RPS26,p.R28*;RPL5,p.R35*;RPL11,p.T44Lfs*40)。本研究包括2名患者，报告了来自4个和6个国家的13例RPS10突变患者和38例RPS26突变患者，分别。RPS10和RPS26突变患者的身体畸形发生率（22％和36％，分别）低于DBA患者的总体发生率（约50％）。与RPS10相比，RPS26突变的患者对类固醇治疗的反应率差（47％vs.87.5%），但首选红细胞输血（67%vs.44%,p=0.0253)。
结论：我们的发现增加了DBA致病变异数据库，并证明了具有RPS10/RPS26突变的DBA患者的临床表现。它表明，下一代测序是诊断DBA等遗传疾病的有力工具。
方法：为了研究新突变的存在，并更深入地了解疾病的分子机制，对12例临床怀疑为DBA的患者进行了靶向下一代测序.到2022年11月，检索到完整的英文临床信息。临床特征，治疗,分析RPS10/RPS26突变。
结果：在12例患者中，鉴定出11个突变,其中5个是新的(RPS19,p.W52S;RPS10,p.P106Qfs*11;RPS26,p.R28*;RPL5,p.R35*;RPL11,p.T44Lfs*40)。本研究包括2名患者，报告了来自4个和6个国家的13例RPS10突变患者和38例RPS26突变患者，分别。RPS10和RPS26突变患者的身体畸形发生率（22％和36％，分别）低于DBA患者的总体发生率（约50％）。与RPS10相比，RPS26突变的患者对类固醇治疗的反应率差（47％vs.87.5%），但首选红细胞输血（67%vs.44%,p=0.0253)。
结论：我们的发现增加了DBA致病变异数据库，并证明了具有RPS10/RPS26突变的DBA患者的临床表现。它表明，下一代测序是诊断DBA等遗传疾病的有力工具。
