Congenital dyserythropoietic anemia type I: First report from the Congenital Dyserythropoietic Anemia Registry of North America (CDAR)

Niss, Omar; Lorsbach, Robert B.; Berger, Mikaela; Chonat, Satheesh; McLemore, Morgan L.; Buchbinder, David; McCavit, Timothy L.; Shaffer, Linda; Simpson, Jessica; Schwartz, Jeffrey H.; Meznarich, Jessica; Emberesh, Myesa; Seu, Katie Giger; Zhang, Wenying; Kalfa, Theodosia A.

doi:10.1016/j.bcmd.2020.102534

Cited by 6 publications

(8 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The establishment of the Congenital Dyserythropoietic Anemia Registry [96] is bound to accelerate the identification of novel CDA-associated genes and increase the need for new in vivo models. In fact, the first such gene is VPS4A [97,98], a regulator of the ESCRT-III complex. Two probands have heterozygous de novo mutations R284W and G203E, and a third carries a homozygous A28V mutation.…”

Section: Discussionmentioning

confidence: 99%

Modeling congenital dyserythropoietic anemia in genetically modified mice

Kumari

Kaźmierczak

2022

Acta Haematol Pol.

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Modeling congenital dyserythropoietic anemia in genetically modified mice

Kumari

Kaźmierczak

2022

Acta Haematol Pol.

View full text Add to dashboard Cite

show abstract

“…Nonhematologic abnormalities have been reported in CDA I, including dysmorphic bone features mostly involving the hand and/or foot (in $10% of patients) [19], short stature [21], osteoporosis, pulmonary hypertension of the newborn [22], and retinal angioid streaks [23]. In addition, left ventricular noncompaction (a form of cardiomyopathy) appears to be more prevalent in CDA I patients compared with age-matched and gender-matched controls [24], independently of the iron storage status; however, the clinical significance of this finding remains unknown, particularly that no adverse clinical cardiac outcome was identified in this study [24].…”

Section: Clinical and Laboratory Characteristicsmentioning

confidence: 99%

The congenital dyserythropoieitic anemias: genetics and pathophysiology

King

Gallagher

Khoriaty

2021

Current Opinion in Hematology

View full text Add to dashboard Cite

Purpose of reviewThe congenital dyserythropoietic anemias (CDA) are hereditary disorders characterized by ineffective erythropoiesis. This review evaluates newly developed CDA disease models, the latest advances in understanding the pathogenesis of the CDAs, and recently identified CDA genes.Recent findingsMice exhibiting features of CDAI were recently generated, demonstrating that Codanin-1 (encoded by Cdan1) is essential for primitive erythropoiesis. Additionally, Codanin-1 was found to physically interact with CDIN1, suggesting that mutations in CDAN1 and CDIN1 result in CDAI via a common mechanism. Recent advances in CDAII (which results from SEC23B mutations) have also been made. SEC23B was found to functionally overlap with its paralogous protein, SEC23A, likely explaining the absence of CDAII in SEC23B-deficient mice. In contrast, mice with erythroid-specific deletion of 3 or 4 of the Sec23 alleles exhibited features of CDAII. Increased SEC23A expression rescued the CDAII erythroid defect, suggesting a novel therapeutic strategy for the disease. Additional recent advances included the identification of new CDA genes, RACGAP1 and VPS4A, in CDAIII and a syndromic CDA type, respectively.SummaryEstablishing cellular and animal models of CDA is expected to result in improved understanding of the pathogenesis of these disorders, which may ultimately lead to the development of new therapies.

show abstract

“…CDAs have been classified into four types (I-IV) (renella Delaunay and Iolascon, 1999 ; Heimpel, 2004 ; Arnaud et al, 2010 ; Iolascon et al, 2013 ). CDA-I is an autosomal recessive disease associated with moderate-to-severe macrocytic anemia and occasional bone abnormalities, particularly syndactyly of fingers and toes, and the absence of nails ( Tamary et al, 1996 , 2005 ; Delaunay and Iolascon, 1999 ; Heimpel et al, 2006 ; Niss et al, 2021 ). Bone marrow aspirates reveal binuclear intermediate and late erythroid precursors, and internuclear chromatin bridges.…”

Section: Introductionmentioning

confidence: 99%

Cdan1 Is Essential for Primitive Erythropoiesis

et al. 2021

View full text Add to dashboard Cite

Congenital dyserythropoietic anemia type I (CDA I) is an autosomal recessive disease characterized by moderate to severe macrocytic anemia and pathognomonic morphologic abnormalities of the erythroid precursors, including spongy heterochromatin. The disease is mainly caused by mutations in CDAN1 (encoding for Codanin-1). No patients with homozygous null type mutations have been described, and mouse null mutants die during early embryogenesis prior to the initiation of erythropoiesis. The cellular functions of Codanin-1 and the erythroid specificity of the phenotype remain elusive. To investigate the role of Codanin-1 in erythropoiesis, we crossed mice carrying the Cdan1 floxed allele (Cdanfl/fl) with mice expressing Cre-recombinase under regulation of the erythropoietin receptor promoter (ErGFPcre). The resulting CdanΔEry transgenic embryos died at mid-gestation (E12.5–E13.5) from severe anemia, with very low numbers of circulating erythroblast. Transmission electron microscopy studies of primitive erythroblasts (E9.5) revealed the pathognomonic spongy heterochromatin. The morphology of CdanΔEry primitive erythroblasts demonstrated progressive development of dyserythropoiesis. Annexin V staining showed increases in both early and late-apoptotic erythroblasts compared to controls. Flow cytometry studies using the erythroid-specific cell-surface markers CD71 and Ter119 demonstrated that CdanΔEry erythroid progenitors do not undergo the semi-synchronous maturation characteristic of primitive erythroblasts. Gene expression studies aimed to evaluate the effect of Cdan1 depletion on erythropoiesis revealed a delay of ζ to α globin switch compared to controls. We also found increased expression of Gata2, Pu.1, and Runx1, which are known to inhibit terminal erythroid differentiation. Consistent with this data, our zebrafish model showed increased gata2 expression upon cdan1 knockdown. In summary, we demonstrated for the first time that Cdan1 is required for primitive erythropoiesis, while providing two experimental models for studying the role of Codanin-1 in erythropoiesis and in the pathogenesis of CDA type I.

show abstract

Congenital dyserythropoietic anemia type I: First report from the Congenital Dyserythropoietic Anemia Registry of North America (CDAR)

Cited by 6 publications

References 56 publications

Modeling congenital dyserythropoietic anemia in genetically modified mice

Modeling congenital dyserythropoietic anemia in genetically modified mice

The congenital dyserythropoieitic anemias: genetics and pathophysiology

Cdan1 Is Essential for Primitive Erythropoiesis

Contact Info

Product

Resources

About