New cases and mutations in SEC23B gene causing congenital dyserythropoietic anemia type II
Autor/a
Mara Musri, Melina
Venturi, Veronica
Ferrer-Cortès, Xènia
Romero-Cortadellas, Lídia
Hernández, Gonzalo
Leoz, Pilar
Ricard Andrés, María Pilar
Morado, Marta
Fernández Valle, María del Carmen
Beneitez Pastor, David
Ortuño Cabrero, Ana
Moreno Gamiz, Maite
Senent Peris, Leonor
Perez-Valencia, Amanda Isabel
Pérez-Montero, Santiago
Tornador, Cristian
Sánchez, Mayka
Fecha de publicación
2023ISSN
1422-0067
Resumen
Congenital dyserythropoietic anemia type II (CDA II) is an inherited autosomal recessive blood disorder which belongs to the wide group of ineffective erythropoiesis conditions. It is characterized by mild to severe normocytic anemia, jaundice, and splenomegaly owing to the hemolytic component. This often leads to liver iron overload and gallstones. CDA II is caused by biallelic mutations in the SEC23B gene. In this study, we report 9 new CDA II cases and identify 16 pathogenic variants, 6 of which are novel. The newly reported variants in SEC23B include three missenses (p.Thr445Arg, p.Tyr579Cys, and p.Arg701His), one frameshift (p.Asp693GlyfsTer2), and two splicing variants (c.1512-2A>G, and the complex intronic variant c.1512-3delinsTT linked to c.1512-16_1512-7delACTCTGGAAT in the same allele). Computational analyses of the missense variants indicated a loss of key residue interactions within the beta sheet and the helical and gelsolin domains, respectively. Analysis of SEC23B protein levels done in patient-derived lymphoblastoid cell lines (LCLs) showed a significant decrease in SEC23B protein expression, in the absence of SEC23A compensation. Reduced SEC23B mRNA expression was only detected in two probands carrying nonsense and frameshift variants; the remaining patients showed either higher gene expression levels or no expression changes at all. The skipping of exons 13 and 14 in the newly reported complex variant c.1512-3delinsTT/c.1512-16_1512-7delACTCTGGAAT results in a shorter protein isoform, as assessed by RT-PCR followed by Sanger sequencing. In this work, we summarize a comprehensive spectrum of SEC23B variants, describe nine new CDA II cases accounting for six previously unreported variants, and discuss innovative therapeutic approaches for CDA II.
Tipo de documento
Artículo
Versión del documento
Versión publicada
Lengua
Inglés
Materias (CDU)
61 - Medicina
Palabras clave
Anèmia diseritropoètica congènita
CDA tipus II; SEC23B
Anèmies hereditàries
Eritropoesi ineficaç
Malaltia rara de la sang
Mutacions
Variants
Anemia diseritropoyética congénita
CDA tipo II
SEC23B
Anemias hereditarias
Eritropoyesis ineficaz
Enfermedad sanguínea rara
Mutaciones
Variantes
Congenital dyserythropoietic anemia
CDA type II
SEC23B
Hereditary anemias
Ineffective erythropoiesis
Rare blood disease
Mutations
Variants
Páginas
19
Publicado por
MDPI
Colección
24;12
Publicado en
International Journal of Molecular Sciences
Citación
Mara Musri, Melina; Venturi, Veronica; Ferrer-Cortès, Xènia [et al.]. New cases and mutations in SEC23B gene causing congenital dyserythropoietic anemia type II. International Journal of Molecular Sciences, 2023, 24(12), 9935. Disponible en: <https://www.mdpi.com/1422-0067/24/12/9935>. Fecha de acceso: 21 sep. 2023. DOI: 10.3390/ijms24129935
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Derechos
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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