CDAII presenting as hydrops foetalis: Molecular characterization of two cases

Fermo, Elisa; Bianchi, Paola; Notarangelo, Lucia Dora; Binda, Silvana; Vercellati, Cristina; Marcello, Anna Paola; Boschetti, Carla; Barcellini, Wilma; Zanella, Alberto

doi:10.1016/j.bcmd.2010.03.005

Cited by 25 publications

(37 citation statements)

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“…9,10 Since then approximately 60 different causative mutations have been described along the gene including missense, nonsense, deletion and splice site mutations; 11 the missense mutations affecting highly conserved residues in multiple domains of SEC23B. [9][10][11][12][13][14][15][16][17] The defect is transmitted as an autosomal recessive trait; in almost all patients, mutations are detected at homozygous or compound heterozygote level. The coexistence of two severe nonsense mutations has never been described suggesting that this condition is most likely lethal.…”

Section: Introductionmentioning

confidence: 99%

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

Satchwell¹,

Pellegrin²,

Bianchi

et al. 2013

Haematologica

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Section: Introductionmentioning

confidence: 99%

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

Satchwell¹,

Pellegrin²,

Bianchi

et al. 2013

Haematologica

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“…95 At present, it appears that most or all cases of CDAII result from biallelic SEC23B mutations. 11,75,[93][94][95] Although only a single heterozygous SEC23B mutation has been identified in some patients, [93][94][95] it is likely that For personal use only. on April 28, 2019. by guest www.bloodjournal.org From the second mutation is located outside of the sequenced region, such as in a distant regulatory sequence or a remote intronic sequence interfering with splicing.…”

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confidence: 99%

“…Only ϳ 10% require regular red cell transfusions in infancy and childhood, 74 and CDAII presenting as hydrops fetalis has been reported. 75 The mean corpuscular volume is typically normal, though …”

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The COPII pathway and hematologic disease

Khoriaty

Vasievich

Ginsburg

2012

Blood

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IntroductionMultiple human diseases resulting from defects in the endoplasmic reticulum (ER)-to-Golgi transport have been reported over the past 14 years (Table 1). Anderson disease or chylomicron retention disorder (CMRD), 1 a disease characterized by malabsorption of lipids from the diet and accumulation of chylomicrons in the enterocytes, results from mutations in SAR1B, a component of coat protein complex II (COPII)-coated vesicles that bud from the surface of the ER and transport cargo proteins to the Golgi apparatus. Patients with CMRD exhibit failure to thrive in infancy, absence of circulating chylomicrons, low levels of plasma cholesterol, and deficiency of fat-soluble vitamins. Mutations in SEC23A, another component of the COPII coat, result in cranio-lenticulosutural-dysplasia (CLSD), 2 an autosomal recessive syndrome characterized by sutural cataracts, late closure of the cranial fontanelles, skeletal abnormalities, and dysmorphic facial features. Only 2 CLSD pedigrees have been reported, each with a different missense mutation. 2,3 Defects in the ER export machinery have been reported to cause 2 hematologic diseases, combined deficiency of coagulation factors V (FV) and VIII (FVIII) (F5F8D) and congenital dyserythropoietic anemia type II (CDAII). F5F8D is characterized by a decrease in FV and FVIII levels to ϳ 10% of normal with generally mild bleeding manifestations. This disorder results from mutations in either LMAN1 4 (lectin mannose-binding protein 1) or MCFD2 5 (multiple coagulation factor deficiency protein 2), 2 genes that encode the components of a specific ER cargo receptor for FV and FVIII. CDAII results from mutation in SEC23B, a paralog of SEC23A in mammals. CDAII is characterized by mild to moderate anemia, bi-or multinucleated erythroblasts, aberrant glycosylation of erythrocyte band 3, and red blood cell (RBC) lysis in some (but not all) acidified normal sera.Although no human diseases resulting from defects in other components of the early secretory pathway have been reported to date, animal models of defects in Sec24B, Sec24C, and Sec24D, have been described [6][7][8] (Table 1), again reflecting a range of manifestations, from no apparent phenotype (zebrafish Sec24C), 8 to a unique neural tube developmental defect (murine Sec24B) 7,12 to characteristic skeletal malformations (zebrafish Sec24D). 8 A general overview of the Mendelian disorders resulting from defects in the membrane trafficking machinery was recently published. 13 In this review, we focus on the 2 hematologic diseases F5F8D indicates combined deficiency of coagulation factors V and VIII; CMRD, chylomicron retention disorder; CLSD, cranio-lenticulo-sutural-dysplasia; CDAII, congenital dyserythropoietic anemia type II; and NR, none reported.*Morphant zebrafish models (where the zebrafish have been treated with a morpholino antisense oligonucleotide to "knockdown" the expression of the gene of interest). †Mutant zebrafish models. 31BLOOD, 5 JULY 2012 ⅐ VOLUME 120, NUMBER 1For personal use only. on April 28, 2019. by gue...

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“…7,8,23 Severe molecular defects in the causative gene SEC23B seem to be the possible cause of this condition, but further studies are requested to demonstrate this. 23 Although this disorder is considered to be congenital, it is interesting that this type of anemia can be diagnosed in all age groups. Diagnosis of CDA II is usually made later in life compared with CDA I, because the symptoms can be milder ( Figure 2).…”

Section: Clinical and Laboratory Findingsmentioning

confidence: 99%

“…Hydrops fetalis has been described in 6 atypical cases which were characterized by erythroblastic multinuclearity but did not fulfil the CDA II diagnostic criteria. 7,8,23 Severe molecular defects in the causative gene SEC23B seem to be the possible cause of this condition, but further studies are requested to demonstrate this. 23 Although this disorder is considered to be congenital, it is interesting that this type of anemia can be diagnosed in all age groups.…”

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Clinical aspects and pathogenesis of congenital dyserythropoietic anemias: from morphology to molecular approach

2012

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Congenital dyserythropoietic anemias belong to a group of inherited conditions characterized by a maturation arrest during erythropoiesis with a reduced reticulocyte production in contrast with erythroid hyperplasia in bone marrow. The latter shows specific morphological abnormalities that allowed for a morphological classification of these conditions mainly represented by congenital dyserythropoietic anemias types I and II. The identification of their causative genes provided evidence that these conditions have different molecular mechanisms that induce abnormal cell maturation and division. Some altered proteins seem to be involved in the chromatin assembly, such as codanin-1 in congenital dyserythropoietic anemia I. The gene involved in congenital dyserythropoietic anemia II, the most frequent form, is SEC23B. This condition seems to belong to a group of diseases attributable to defects in the transport of newly synthesized proteins from endoplasmic reticulum to the Golgi. This review will analyze recent insights in congenital dyserythropoietic anemias types I and II. It will also attempt to clarify the relationship between mutations in causative genes and the clinical phenotype of these conditions. Key words: dyserythropoiesis, congenital dyserythropoietic anemia, red blood cells, inherited anemias.Citation: Iolascon A, Esposito MR, and Russo R. Clinical aspects and pathogenesis of congenital dyserythropoietic anemias: from morphology to molecular approach. Haematologica 2012;97(12): 1786-1794. doi:10.3324/haematol.2012 This is an open-access paper. ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o nto distinguish without molecular evaluation. 7,8 Recent identification of several causative genes could help reclassify these disorders (Table 1). Variant forms are very rare and this, up to now, has compromised further molecular studies. Linkage studies had previously been the main tool to clarify the genetics of Mendelian disorders; however, extremely rare disorders or sporadic cases caused by de novo variants are not appropriate for this type of study design. Exome sequencing is now becoming technically feasible and more cost-effective due to the recent advances in high-throughput sequence capture methods and next-generation sequencing technologies that have offered new opportunities for research into Mendelian disorders. 9 We suggest that the use of these new technologies will lead to the identification of new causative genes in CDA variants in the near future. In particular, this review will deal with new insights on the two most frequent forms of CDAs: types I and II. Epidemiology of CDAsUntil December 2011, 712 cases from 614 families were included in the German CDA Registry, 10,11 whereas 206Clinical aspects and pathogenesis of CDAs haematologica | 2012; 97 (12) 1787 © F e r r a t a S t o r t i F o u n d a t i o ncases from 183 families were enrolled in the Italian CDA registry (A Iolascon, unpublished data, 2011 Although CDA II patients are to be found right across the Italian peninsula, the maj...

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CDAII presenting as hydrops foetalis: Molecular characterization of two cases

Cited by 25 publications

References 18 publications

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

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

The COPII pathway and hematologic disease

Clinical aspects and pathogenesis of congenital dyserythropoietic anemias: from morphology to molecular approach

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