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Annals of Hematology
Published in: Annals of Hematology 2/2021

01-02-2021 | Anemia | Original Article

Congenital dyserythropoietic anemia types Ib, II, and III: novel variants in the CDIN1 gene and functional study of a novel variant in the KIF23 gene

Authors: Manuel Méndez, María Isabel Moreno-Carralero, Valeria L. Peri, Rafael Camacho-Galán, José M. Bosch-Benítez, Jorge Huerta-Aragonés, Jorge Sánchez-Calero-Guilarte, María Belén Moreno-Risco, Juan Manuel Alonso-Domínguez, María José Morán-Jiménez

Published in: Annals of Hematology | Issue 2/2021

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Abstract

Congenital dyserythropoietic anemias (CDA) are disorders characterized by ineffective erythropoiesis and morphological anomalies in erythrocytes and erythroblasts. The purpose of this study is to identify the gene variants in patients diagnosed with CDA. We analyzed five unrelated patients and two siblings with a targeted panel of genes to CDA: CDAN1, CDIN1, SEC23B, KIF23, KLF1, and GATA1 genes. We found three novel variants in the CDIN1 gene (p.Leu136Val, p.Tyr247Cys, and p.Ile273Thr), four known variants in the SEC23B gene (p.Arg14Trp, p.Arg554Ter, p.Asp239Gly, and p.Ser436Leu), and one novel variant in the KIF23 gene (p.Leu945Trpfs*31). The in silico analysis of novel variants predict that they are pathogenic and, the in vitro study confirms the functional impact of the KIF23 variant on the protein location.
Literature
1.
Gambale A, Iolascon A, Andolfo I, Russo R (2016) Diagnosis and management of congenital dyserythropoietic anemias. Expert Rev Hematol 9(3):283–296PubMed
2.
Babbs C, Roberts NA, Sanchez-Pulido L, McGowan SJ, Ahmed MR, Brown JM, Sabry MA, Consortium WGS, Bentley DR, McVean GA, Donnelly P, Gileadi O, Ponting CP, Higgs DR, Buckle VJ (2013) Homozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type I. Haematologica 98(9):1383–1387PubMedPubMedCentral
3.
4.
5.
Russo R, Andolfo I, Manna F, Gambale A, Marra R, Rosato BE, Caforio P, Pinto V, Pignataro P, Radhakrishnan K, Unal S, Tomaiuolo G, Forni GL, Iolascon A (2018) Multi-gene panel testing improves diagnosis and management of patients with hereditary anemias. Am J Hematol 93(5):672–682PubMed
6.
Wang Y, Ru Y, Liu G, Dong S, Li Y, Zhu X, Zhang F, Chang YZ, Nie G (2018) Identification of CDAN1, C15ORF41 and SEC23B mutations in Chinese patients affected by congenital dyserythropoietic anemia. Gene 640:73–78PubMed
7.
Russo R, Marra R, Andolfo I, De Rosa G, Rosato BE, Manna F, Gambale A, Raia M, Unal S, Barella S, Iolascon A (2019) Characterization of two cases of congenital dyserythropoietic anemia type I shed light on the uncharacterized C15orf41 protein. Front Physiol 10:621PubMedPubMedCentral
8.
Russo R, Gambale A, Langella C, Andolfo I, Unal S, Iolascon A (2014) Retrospective cohort study of 205 cases with congenital dyserythropoietic anemia type II: definition of clinical and molecular spectrum and identification of new diagnostic scores. Am J Hematol 89(10):E169–E175PubMed
9.
Bianchi P, Schwarz K, Hogel J, Fermo E, Vercellati C, Grosse R, van Wijk R, van Zwieten R, Barcellini W, Zanella A, Heimpel H (2016) Analysis of a cohort of 101 CDAII patients: description of 24 new molecular variants and genotype-phenotype correlations. Br J Haematol 175(4):696–704PubMed
10.
Sandstrom H, Wahlin A (2000) Congenital dyserythropoietic anemia type III. Haematologica 85(7):753–757PubMed
11.
Accame EA, de Tezanos Pinto M (1981) Congenital dyserythropoiesis with erythroblastic polyploidy. Report of a variety found in Argentinian Mesopotamia (author’s transl). Sangre (Barc) 26(5-A):545–555
12.
Bergstrom I, Jacobsson L (1962) Hereditary benign erythroreticulosis. Blood 19:296–303PubMed
13.
Sandstrom H, Wahlin A, Eriksson M, Bergstrom I (1994) Serum thymidine kinase in congenital dyserythropoietic anaemia type III. Br J Haematol 87(3):653–654PubMed
14.
Sandstrom H, Wahlin A, Eriksson M, Bergstrom I, Wickramasinghe SN (1994) Intravascular haemolysis and increased prevalence of myeloma and monoclonal gammopathy in congenital dyserythropoietic anaemia, type III. Eur J Haematol 52(1):42–46PubMed
15.
Sandstrom H, Wahlin A, Eriksson M, Holmgren G, Lind L, Sandgren O (1997) Angioid streaks are part of a familial syndrome of dyserythropoietic anaemia (CDA III). Br J Haematol 98(4):845–849PubMed
16.
Wickramasinghe SN, Parry TE, Williams C, Bond AN, Hughes M, Crook S (1982) A new case of congenital dyserythropoietic anaemia, type III: studies of the cell cycle distribution and ultrastructure of erythroblasts and of nucleic acid synthesis in marrow cells. J Clin Pathol 35(10):1103–1109PubMedPubMedCentral
17.
Wickramasinghe SN, Wahlin A, Anstee D, Parsons SF, Stopps G, Bergstrom I, Eriksson M, Sandstrom H, Shiels S (1993) Observations on two members of the Swedish family with congenital dyserythropoietic anaemia, type III. Eur J Haematol 50(4):213–221PubMed
18.
Wolff JA, Von Hofe FH (1951) Familial erythroid multinuclearity. Blood 6(12):1274–1283PubMed
19.
Byrnes RK, Dhru R, Brady AM, Galen WP, Hopper B (1980) Congenital dyserythropoietic anemia in treated Hodgkin’s disease. Hum Pathol 11(5):485–486PubMed
20.
Carreno-Tarragona G, Trapiello-Valbuena F, Aranda-Salom J, Martinez-Lopez J, Lumbreras C, Oliveira-Ramirez E, Diaz-Pedroche C (2015) Antiphospholipid syndrome in a patient suffering from congenital dyserythropoietic anemia type III. Ann Hematol 94(8):1411–1412PubMed
21.
Choudhry VP, Saraya AK, Kasturi J, Rath PK (1981) Congenital dyserythropoietic anaemias: splenectomy as a mode of therapy. Acta Haematol 66(3):195–201PubMed
22.
Clauvel JP, Cosson A, Breton-Gorius J, Flandrin G, Faille A, Bonnet-Gajdos M, Turpin F, Bernard J (1972) Congenital dyserythropoiesis (study of 6 cases). Nouv Rev Fr Hematol 12(5):653–672PubMed
23.
Goudsmit R, Beckers D, De Bruijne JI, Engelfriet CP, James J, Morselt AF, Reynierse E (1972) Congenital dyserythropoietic anaemia, type 3. Br J Haematol 23(1):97–105PubMed
24.
Krouwels FH, Bresser P, von dem Borne AE (1999) Extramedullary hematopoiesis: breathtaking and hair-raising. N Engl J Med 341(22):1702–1704PubMed
25.
McCluggage WG, Hull D, Mayne E, Bharucha H, Wickramasinghe SN (1996) Malignant lymphoma in congenital dyserythropoietic anaemia type III. J Clin Pathol 49(7):599–602PubMedPubMedCentral
26.
Morales R, Pérez-de-Soto I, Sánchez J, Fernández R, Prats C, De-Blas J, Caballero T, Herrera A, Carrillo E, Calderón C, Bernal R, Martin Noya A, Pérez-Simón JA Anemia diseritropoyética congénita tipo III: nuevo caso esporádico con algunas peculiaridades citomorfológicas. LV Congreso Nacional de la Sociedad Española de Hematología y Hemoterapia Simposios Sevilla, Spain. Octuber 17-19, 2015:209-214
27.
Sigler E, Shaft D, Shtalrid M, Shvidel L, Berrebi A, Resnitzky P (2002) New sporadic case of congenital dyserythropoietic anemia type III in an aged woman: detailed description of ultrastructural findings. Am J Hematol 70(1):72–76PubMed
28.
Lind L, Sandstrom H, Wahlin A, Eriksson M, Nilsson-Sojka B, Sikstrom C, Holmgren G (1995) Localization of the gene for congenital dyserythropoietic anemia type III, CDAN3, to chromosome 15q21-q25. Hum Mol Genet 4(1):109–112PubMed
29.
Liljeholm M, Irvine AF, Vikberg AL, Norberg A, Month S, Sandstrom H, Wahlin A, Mishima M, Golovleva I (2013) Congenital dyserythropoietic anemia type III (CDA III) is caused by a mutation in kinesin family member, KIF23. Blood 121(23):4791–4799PubMed
30.
Arnaud L, Saison C, Helias V, Lucien N, Steschenko D, Giarratana MC, Prehu C, Foliguet B, Montout L, de Brevern AG, Francina A, Ripoche P, Fenneteau O, Da Costa L, Peyrard T, Coghlan G, Illum N, Birgens H, Tamary H, Iolascon A, Delaunay J, Tchernia G, Cartron JP (2010) A dominant mutation in the gene encoding the erythroid transcription factor KLF1 causes a congenital dyserythropoietic anemia. Am J Hum Genet 87(5):721–727PubMedPubMedCentral
31.
de-la Iglesia-Inigo S, Moreno-Carralero MI, Lemes-Castellano A, Molero-Labarta T, Mendez M, Moran-Jimenez MJ (2017) A case of congenital dyserythropoietic anemia type IV. Clin Case Rep 5(3):248–252
32.
Jaffray JA, Mitchell WB, Gnanapragasam MN, Seshan SV, Guo X, Westhoff CM, Bieker JJ, Manwani D (2013) Erythroid transcription factor EKLF/KLF1 mutation causing congenital dyserythropoietic anemia type IV in a patient of Taiwanese origin: review of all reported cases and development of a clinical diagnostic paradigm. Blood Cells Mol Dis 51(2):71–75PubMedPubMedCentral
33.
Ortolano R, Forouhar M, Warwick A, Harper D (2018) A case of congenital dyserythropoeitic anemia type IV caused by E325K mutation in erythroid transcription factor KLF1. J Pediatr Hematol Oncol 40(6):e389–e391PubMed
34.
Ravindranath Y, Johnson RM, Goyette G, Buck S, Gadgeel M, Gallagher PG (2018) KLF1 E325K-associated congenital dyserythropoietic anemia type IV: insights into the variable clinical severity. J Pediatr Hematol Oncol 40(6):e405–e409PubMedPubMedCentral
35.
36.
Ahmed MS, Shahjaman M, Kabir E, Kamruzzaman M (2018) Structure modeling to function prediction of uncharacterized human protein C15orf41. Bioinformation 14(5):206–212PubMedPubMedCentral
37.
Aydin Koker S, Karapinar TH, Oymak Y, Bianchi P, Fermo E, Gozmen S, Vergin C (2018) Identification of a novel mutation in the SEC23B gene associated with congenital dyserythropoietic anemia type II through the use of next-generation sequencing panel in an undiagnosed case of nonimmune hereditary hemolytic anemia. J Pediatr Hematol Oncol 40(7):e421–e423PubMed
38.
Bianchi P, Fermo E, Vercellati C, Boschetti C, Barcellini W, Iurlo A, Marcello AP, Righetti PG, Zanella A (2009) Congenital dyserythropoietic anemia type II (CDAII) is caused by mutations in the SEC23B gene. Hum Mutat 30(9):1292–1298PubMed
39.
Iolascon A, Russo R, Esposito MR, Asci R, Piscopo C, Perrotta S, Feneant-Thibault M, Garcon L, Delaunay J (2010) Molecular analysis of 42 patients with congenital dyserythropoietic anemia type II: new mutations in the SEC23B gene and a search for a genotype-phenotype relationship. Haematologica 95(5):708–715PubMed
40.
Punzo F, Bertoli-Avella AM, Scianguetta S, Della Ragione F, Casale M, Ronzoni L, Cappellini MD, Forni G, Oostra BA, Perrotta S (2011) Congenital dyserythropoietic anemia type II: molecular analysis and expression of the SEC23B gene. Orphanet J Rare Dis 6:89PubMedPubMedCentral
41.
Russo R, Esposito MR, Asci R, Gambale A, Perrotta S, Ramenghi U, Forni GL, Uygun V, Delaunay J, Iolascon A (2010) Mutational spectrum in congenital dyserythropoietic anemia type II: identification of 19 novel variants in SEC23B gene. Am J Hematol 85(12):915–920PubMedPubMedCentral
42.
Russo R, Gambale A, Esposito MR, Serra ML, Troiano A, De Maggio I, Capasso M, Luzzatto L, Delaunay J, Tamary H, Iolascon A (2011) Two founder mutations in the SEC23B gene account for the relatively high frequency of CDA II in the Italian population. Am J Hematol 86(9):727–732PubMedPubMedCentral
43.
Schwarz K, Iolascon A, Verissimo F, Trede NS, Horsley W, Chen W, Paw BH, Hopfner KP, Holzmann K, Russo R, Esposito MR, Spano D, De Falco L, Heinrich K, Joggerst B, Rojewski MT, Perrotta S, Denecke J, Pannicke U, Delaunay J, Pepperkok R, Heimpel H (2009) Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type II. Nat Genet 41(8):936–940PubMed
44.
Moreno-Carralero MI, Horta-Herrera S, Morado-Arias M, Ricard-Andres MP, Lemes-Castellano A, Abio-Calvete M, Cedena-Romero MT, Gonzalez-Fernandez FA, Llorente-Gonzalez L, Periago-Peralta AM, de-la-Iglesia-Inigo S, Mendez M, Moran-Jimenez MJ (2018) Clinical and genetic features of congenital dyserythropoietic anemia (CDA). Eur J Haematol 101(3):368–378PubMed
45.
Amir A, Dgany O, Krasnov T, Resnitzky P, Mor-Cohen R, Bennett M, Berrebi A, Tamary H (2011) E109K is a SEC23B founder mutation among Israeli Moroccan Jewish patients with congenital dyserythropoietic anemia type II. Acta Haematol 125(4):202–207PubMed
46.
47.
Deavours BE, Walker RA (1999) Nuclear localization of C-terminal domains of the kinesin-like protein MKLP-1. Biochem Biophys Res Commun 260(3):605–608PubMed
48.
Liu X, Erikson RL (2007) The nuclear localization signal of mitotic kinesin-like protein Mklp-1: effect on Mklp-1 function during cytokinesis. Biochem Biophys Res Commun 353(4):960–964PubMed
49.
Perez-Jacoiste Asin MA, Ruiz Robles G (2016) Skull erythropoiesis in a patient with congenital dyserythropoietic anaemia. Lancet 387(10020):787PubMed
Metadata
Title
Congenital dyserythropoietic anemia types Ib, II, and III: novel variants in the CDIN1 gene and functional study of a novel variant in the KIF23 gene
Authors
Manuel Méndez
María Isabel Moreno-Carralero
Valeria L. Peri
Rafael Camacho-Galán
José M. Bosch-Benítez
Jorge Huerta-Aragonés
Jorge Sánchez-Calero-Guilarte
María Belén Moreno-Risco
Juan Manuel Alonso-Domínguez
María José Morán-Jiménez
Publication date
01-02-2021
Publisher
Springer Berlin Heidelberg
Keyword
Anemia
Published in
Annals of Hematology / Issue 2/2021
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-020-04319-5

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