Congenital dyserythropoietic anaemias: clinical features, haematological morphology and new biochemical data

Wickramasinghe, S. N.

doi:10.1016/s0268-960x(98)90016-9

Cited by 103 publications

(105 citation statements)

References 92 publications

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“…Dysplastic signs include markedly irregular nuclei with frequent (3.5%-7%) binucleate erythroblasts (particularly late cells) and occasional trinucleate and tetranucleate cells. 8 None of these morphologic abnormalities is entirely specific for CDA-1 as they can be found in the other CDA types and in other acquired dyserythropoietic states. 9 Particular diagnostic findings in CDA-1 are the presence in the marrow of internuclear bridges between intermediate erythroblasts (ϳ 3% of total erythroblasts) and a characteristic pattern of spongy "Swiss cheese" heterochromatin as observed by electron microscopy.…”

Section: Introductionmentioning

confidence: 99%

Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1α localization in erythroblasts

Renella

Roberts

Brown

et al. 2011

Blood

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Congenital dyserythropoietic anemia type 1 (CDA-1), a rare inborn anemia characterized by abnormal chromatin ultrastructure in erythroblasts, is caused by abnormalities in codanin-1, a highly conserved protein of unknown function. We have produced 3 monoclonal antibodies to codanin-1 that demonstrate its distribution in both nucleus and cytoplasm by immunofluorescence and allow quantitative measurements of patient and normal material by Western blot. A detailed analysis of chromatin structure in CDA-1 erythroblasts shows no abnormalities in overall histone composition, and the genomewide epigenetic landscape of several histone modifications is maintained. However, immunofluorescence analysis of intermediate erythroblasts from patients with CDA-1 reveals abnormal accumulation of HP1␣ in the Golgi apparatus. A link between mutant codanin-1 and the aberrant localization of HP1␣ is supported by the finding that codanin-1 can be coimmunoprecipitated by anti-HP1␣ antibodies. Furthermore, we show colocalization of codanin-1 with Sec23B, the protein defective in CDA-2 suggesting that the CDAs might be linked at the molecular level. Mice containing a gene-trapped Cdan1 locus demonstrate its widespread expression during development. Cdan1 gt/gt homozygotes die in utero before the onset of primitive erythropoiesis, suggesting that Cdan1 has other critical roles during embryogenesis. (Blood. 2011;117(25): 6928-6938) IntroductionThe congenital dyserythropoietic anemias (CDAs) are a heterogeneous group of rare inborn disorders mainly affecting erythropoiesis. 1 Distinct from other inherited bone marrow failure syndromes, they are marked by morphologic abnormalities of the erythroblasts that lead to ineffective erythropoiesis/dyserythropoiesis, whereas the other hematopoietic lineages appear to be unaffected. Based largely on the dysplastic changes observed in erythroblasts by light and electron microscopy, the CDAs have been divided into 3 major types, designated CDA types 1, 2, and 3 2 ; causative genes have been identified for CDA-1 (CDAN1/codanin-1) 3 and CDA-2 (CDAN2/Sec23B), 4 whereas only the chromosomal locus is known for . 5 In CDA-1, the majority of cases come to attention during childhood and adolescence, often within episodes of erythropoietic stress (ie, infection, and in young women, pregnancy). 6,7 Severe presentations can include gallstones, chronic hyperbilirubinemia, and/or extramedullary hematopoietic foci in the parietal and frontal bones of the skull (as observed in thalassemia). Although iron overloading is rarely the revelatory sign, it seems to be present in the majority of patients after childhood. In some cases, skeletal or other dysmorphic features can be identified, including short stature, distal limb and nail malformations, vertebral deformations/dysplasias, and skin pigmentation defects. 1 The anemia is macrocytic with mean corpuscular volumes up to 120 fL, and the blood smear shows anisopoikilocytosis, basophilic stippling, and an inadequate reticulocyte response compared with hemolytic anemias....

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Section: Introductionmentioning

confidence: 99%

Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1α localization in erythroblasts

Renella

Roberts

Brown

et al. 2011

Blood

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“…4,5 Confirmation of the diagnosis of CDA I required a mutation of the CDAN1-gene and/ or typical aberrations seen by electron microscopy. 2,6 Confirmation of the diagnosis of CDA II required a mutation of the SEC23B-gene or at least one of the following parameters: positive acid serum lysis test with ABO-compatible sera, 7 a typical abnormality of band 3 shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), 8,9 or a discontinuous double membrane in mature erythroblasts seen by electron microscopy. 2 Specimens of 19 (5 males, 14 females) and 36 patients (21 males, 15 females) with CDAI and CDA II, respectively, were available.…”

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confidence: 99%

The morphological diagnosis of congenital dyserythropoietic anemia: results of a quantitative analysis of peripheral blood and bone marrow cells

Heimpel¹,

Kellermann²,

Neuschwander³

et al. 2010

Haematologica

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“…23 Lesions of both C15ORF41 and CDAN1 cause similar lineage-specific phenotypic abnormalities that result in the clinical presentation of CDA-I. In cases of CDA-I caused by CDAN1 mutations the severity of the anemia varies within and between families, 24,25 and in addition, there is variation in the iron overload arising as a complication. 24,26 The severity of CDA-I caused by C15ORF41 lesions also varies and, in the 3 pedigrees reported here, is comparable with that caused by CDAN1 mutations.…”

Section: Resultsmentioning

confidence: 99%

“…In cases of CDA-I caused by CDAN1 mutations the severity of the anemia varies within and between families, 24,25 and in addition, there is variation in the iron overload arising as a complication. 24,26 The severity of CDA-I caused by C15ORF41 lesions also varies and, in the 3 pedigrees reported here, is comparable with that caused by CDAN1 mutations. Patients with CDA-I caused by C15ORF41 mutations show significant hematologic response to interferon-α, with improved Hb levels and decreased dyserythropoiesis.…”

Section: Resultsmentioning

confidence: 99%

Homozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type I

et al. 2013

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Congenital dyserythropoietic anaemias: clinical features, haematological morphology and new biochemical data

Cited by 103 publications

References 92 publications

Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1α localization in erythroblasts

Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1α localization in erythroblasts

The morphological diagnosis of congenital dyserythropoietic anemia: results of a quantitative analysis of peripheral blood and bone marrow cells

Homozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type I

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