دورية أكاديمية
New Cases and Mutations in SEC23B Gene Causing Congenital Dyserythropoietic Anemia Type II
| العنوان: | New Cases and Mutations in SEC23B Gene Causing Congenital Dyserythropoietic Anemia Type II |
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| المؤلفون: | Musri, Melina Mara, Venturi, Veronica, Ferrer, Xènia, Romero Cortadellas, Lídia, Hernandez Viedma, Gonzalo, Leoz Allegretti, María del Pilar, Beneitez Pastor, David, Ortuño Cabrero, Ana |
| المساهمون: | Institut Català de la Salut, Musri MM BloodGenetics S.L. Diagnostics in Inherited Blood Diseases, Esplugues de Llobregat, Spain. Venturi V, Romero-Cortadellas L Department of Basic Sciences, Iron Metabolism: Regulation and Diseases Group, Universitat Internacional de Catalunya, Sant Cugat del Vallès, Spain. Ferrer-Cortès X, Hernández G BloodGenetics S.L. Diagnostics in Inherited Blood Diseases, Esplugues de Llobregat, Spain. Department of Basic Sciences, Iron Metabolism: Regulation and Diseases Group, Universitat Internacional de Catalunya, Sant Cugat del Vallès, Spain. Leoz P Red Blood Cell Disorders Unit, Department of Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Beneitez Pastor D, Ortuño Cabrero A Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Scientia |
| بيانات النشر: | MDPI |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Anèmia - Aspectes genètics, Sang - Malalties - Aspectes genètics, Eritròcits, Anomalies cromosòmiques, DISEASES::Hemic and Lymphatic Diseases::Hematologic Diseases::Anemia::Anemia, Hemolytic::Anemia, Hemolytic, Congenital::Anemia, Dyserythropoietic, Congenital, Other subheadings::Other subheadings::Other subheadings::/genetics, PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation, ENFERMEDADES::enfermedades hematológicas y linfáticas::enfermedades hematológicas::anemia::anemia hemolítica::anemia hemolítica congénita::anemia diseritropoyética congénita, Otros calificadores::Otros calificadores::Otros calificadores::/genética, FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación |
| الوصف: | Hereditary anemias; Ineffective erythropoiesis; Rare blood disease ; Anèmies hereditàries; Eritropoesi ineficaç; Malaltia rara de la sang ; Anemias hereditarias; Eritropoyesis ineficaz; Enfermedad rara de la sangre ; 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. ; This work was supported by ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| العلاقة: | International Journal of Molecular Sciences;24(12); https://doi.org/10.3390/ijms24129935Test; info:eu-repo/grantAgreement/EC/H2020/894737; Musri MM, Venturi V, Ferrer-Cortès X, Romero-Cortadellas L, Hernández G, Leoz P, et al. New Cases and Mutations in SEC23B Gene Causing Congenital Dyserythropoietic Anemia Type II. Int J Mol Sci. 2023 Jun 9;24(12):9935.; https://hdl.handle.net/11351/9938Test |
| DOI: | 10.3390/ijms24129935 |
| الإتاحة: | https://doi.org/10.3390/ijms24129935Test https://hdl.handle.net/11351/9938Test |
| حقوق: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.38231498 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14220067 |
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| DOI: | 10.3390/ijms24129935 |