Clinical and molecular variability in congenital dyserythropoietic anaemia type I.

Paediatric Haematology Laboratory, Felsenstein Medical Research Centre, Beilinson Campus, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Israel.
British Journal of Haematology (Impact Factor: 4.94). 08/2005; 130(4):628-34. DOI: 10.1111/j.1365-2141.2005.05642.x
Source: PubMed

ABSTRACT Congenital dyserythropoietic anaemia (CDA) type I is a rare, inherited disorder characterised by ineffective erythropoiesis and macrocytic anaemia. Complex bone disease has only occasionally been associated with this disease. CDA I is caused by mutations in the CDAN1 gene encoding for codanin-1. Our aim was to characterise the CDAN1 mutation in eight unrelated patients with sporadic CDA I, three of whom had complex bone disease. Six novel mutations in the CDAN1 gene were identified. In two patients, one mutation and in another, both mutations were elusive. No patient was homozygous for a null-type mutation. However, one patient with complex bone disease was homozygous for a splice-site mutation (IVS-12+5G>A). Western blotting revealed that codanin-1 synthesis was 65% less than the control. Five single nucleotide polymorphisms (SNPs) previously unreported in the literature or the SNP database were also identified. Although the absence of codanin-1 is probably lethal, the presence of 35% of the protein was compatible with life but was associated with severe clinical manifestations. However, in most patients studied, no correlation could be established between the expected levels of codanin-1 or the nature of the mutation and the severity of the clinical manifestations.

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    ABSTRACT: The congenital dyserythropoietic anemias (CDAs) are a heterogeneous group of genetic disorders of red cell production. They are characterized by ineffective erythropoiesis and dyserythropoiesis. Here, we present the clinical description and mutation analysis of a Japanese female with CDA type 1. She has long been diagnosed with unclassified congenital hemolytic anemia from the neonatal period. However, bone marrow morphology and genetic testing of the CDAN1 gene at the age of 12 years confirmed the afore-mentioned diagnosis. Thus, we should be aware of the possibility of CDA if the etiology of congenital anemia or jaundice cannot be clearly elucidated.
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    ABSTRACT: The congenital dyserythropoietic anemias (CDAs) are hereditary disorders characterized by distinct morphological abnormalities of marrow erythroblasts. The unveiling of the genes mutated in the major CDA subgroups (I-CDAN1, II-SEC23B) has now been completed with the recent identification of the CDA III gene (KIF23). KIF23 encodes mitotic kinesin-like protein 1 which plays a critical role in cytokinesis, while the cellular role of the proteins encoded by CDAN1 and SEC23B is still unknown. CDA variants with mutations in erythroid transcription factors genes (KLF1, GATA-1) have been recently identified. Molecular diagnosis of CDA is now possible in most patients.
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