Congenital Dyserythropoietic Anemias: NGS Transforms Diagnosis of Rare Inherited Anemias
This review covers the three major types of congenital dyserythropoietic anemia and their molecular genetics, highlighting how next-generation sequencing has revolutionised diagnosis by reducing time to identification and improving differential diagnosis through discovery of new causative genes. Advances in understanding iron metabolism via erythroferrone-hepcidin signalling have clarified the pathogenesis of hepatic iron overload in CDA type II. The authors also discuss emerging cellular and animal models and potential future therapeutic approaches.
The original study
Congenital dyserythropoietic anemias.
- Authors
- Iolascon A, Andolfo I, Russo R
- Journal
- Blood
- Type
- Journal Article, Research Support, Non-U.S. Gov't, Review
- PMID
- 32702750
Original abstract
Congenital dyserythropoietic anemias (CDAs) are a heterogeneous group of inherited anemias that affect the normal differentiation-proliferation pathways of the erythroid lineage. They belong to the wide group of ineffective erythropoiesis conditions that mainly result in monolinear cytopenia. CDAs are classified into the 3 major types (I, II, III), plus the transcription factor-related CDAs, and the CDA variants, on the basis of the distinctive morphological, clinical, and genetic features. Next-generation sequencing has revolutionized the field of diagnosis of and research into CDAs, with reduced time to diagnosis, and ameliorated differential diagnosis in terms of identification of new causative/modifier genes and polygenic conditions. The main improvements regarding CDAs have been in the study of iron metabolism in CDAII. The erythroblast-derived hormone erythroferrone specifically inhibits hepcidin production, and its role in the mediation of hepatic iron overload has been dissected out. We discuss here the most recent advances in this field regarding the molecular genetics and pathogenic mechanisms of CDAs, through an analysis of the clinical and molecular classifications, and the complications and clinical management of patients. We summarize also the main cellular and animal models developed to date and the possible future therapies.