Correlation of genotype, phenotype and treatment efficacy of Diamond-Blackfan anemia

Abstract

Objective 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 DBA patients.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. Key words: Diamond-Blackfan anemia; Ribosomal protein gene; Genotype; Phenotype; Treatment