Advances in the understanding of the congenital dyserythropoietic anaemias

Abstract

SummaryThe congenital dyserythropoietic anaemias (CDAs) are a heterogeneous group of diseases in which the anaemia is predominantly caused by dyserythropoiesis and marked ineffective erythropoiesis; three major (types I, II and III) and several minor subgroups have been identified. Additional information on the natural history of these conditions, the beneficial role of splenectomy in CDA type II and efficacy of interferon-a in type I have recently been reported. A disease gene has been localised to a chromosomal segment in the three major types and in CDA type I, a disease gene has been identified (CDANI). Mutations have been detected in both familial and sporadic cases but the predicted protein structure gives few clues as to its function. In both type I and II, there are cases unlinked to the identified localisations, suggesting genetic heterogeneity.

Characteristic phenotypes associated with congenital dyserythropoietic anemia (type II) manifest at different stages of erythropoiesis

“…1,44,50,51 We saw no evidence of these structures in our in vitro cultured erythroblasts from the specific CDAII patient's peripheral blood samples we obtained. One possible explanation is that erythroblasts exhibiting this aspect of the disease phenotype do not persist outside of the protective microenvironment of the bone marrow.…”

Congenital dyserythropoietic anemia type III (CDA III) is caused by a mutation in kinesin family member, KIF23

“…Three major types (I, II, and III) and several subtypes have been described. [1][2][3] CDA III is the rarest form of the 3 classical CDAs, with about 60 cases described globally, the majority belonging to a family in Sweden. The disease is characterized by intravascular hemolysis in combination with dyserythropoiesis with large multinucleated erythroblasts (gigantoblasts) in the bone marrow.…”

Human promoter mutations unveil Oct-1 and GATA-1 opposite action on Gfi1b regulation

“…We also analyzed eight myelodisplastic syndromes; two myelofibrosis; five congenital dyserythropoietic anemia (CDA) type II; one CDA type III; one case of "variant CDA type II" with negative Ham test [8,9]; one case of CDA with thrombocytopenia; one congenital sideroblastic anemia (the last three patients had normal GATA-1 by exon sequencing; data non shown); 36 patients with thrombocytosis (platelets between 429 and 1,437 10 3 /μl), 15 of them with JAK 2 V617F mutation, detected as described [10], and 31 with polyglobulia, 22 males with hemoglobin (Hb) range 17.7 to 18.6 g/dl and 9 females with Hb between 15.2 and 19.4 g/dl. Only ten individuals with polyglobulia had JAK 2 V617F mutation that confirmed the diagnosis of polycythemia vera; the other cases were studied to investigate the involvement of Gfi1b promoter single nucleotide polymorphisms (SNPs) in polyglobulias that cannot be classified as myeloproliferative disorders.…”