Identification of novel mutations in patients with Diamond‐Blackfan anemia and literature review of RPS10 and RPS26 mutations

Abstract Introduction 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). Conclusion 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.