Whole-exome analysis to detect congenital hemolytic anemia mimicking congenital dyserythropoietic anemia
Congenital dyserythropoietic anemia (CDA) is a heterogeneous group of rare congenital disorders characterized by ineffective erythropoiesis and dysplastic changes in erythroblasts. Diagnosis of CDA is based primarily on the morphology of bone marrow erythroblasts; however, genetic tests have recently become more important. Here, we performed genetic analysis of 10 Japanese patients who had been diagnosed with CDA based on laboratory findings and morphological characteristics. We examined 10 CDA patients via central review of bone marrow morphology and genetic analysis for congenital bone marrow failure syndromes. Sanger sequencing for CDAN1, SEC23B, and KLF1 was performed for all patients. We performed whole-exome sequencing in patients without mutation in these genes. Three patients carried pathogenic CDAN1 mutations, whereas no SEC23B mutations were identified in our cohort. WES unexpectedly identified gene mutations known to cause congenital hemolytic anemia in two patients: canonical G6PD p.Val394Leu mutation and SPTA1 p.Arg28His mutation. Comprehensive genetic analysis is warranted for more effective diagnosis of patients with suspected CDA.
KeywordsCongenital dyserythropoietic anemia Congenital hemolytic anemia Whole-exome analysis
The authors would like to thank all the clinicians and the patients and families who made this study possible by providing clinical samples. The authors would also like to thank Yoshie Miura, Yuko Imanishi, and Hiroe Namizaki for their valuable assistance. The authors acknowledge the Division for Medical Research Engineering, Nagoya University Graduate School of Medicine for technical support for next-generation sequencing.
This work was supported by the Research on Measures for Intractable Diseases Project from Ministry of Health, Labor, and Welfare and a Grant-in-Aid from the Ministry of Health, Labor, and Welfare of Japan (H23-TA012).
Compliance with ethical standards
Conflict of interest
The authors declare no competing financial interests.
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