Usefulness of NGS for Diagnosis of Dominant Beta-Thalassemia and Unstable Hemoglobinopathies in Five Clinical Cases
| Autor: | Valeria Rizzuto, Tamara T. Koopmann, Adoración Blanco-Álvarez, Barbara Tazón-Vega, Amira Idrizovic, Cristina Díaz de Heredia, Rafael Del Orbe, Miriam Vara Pampliega, Pablo Velasco, David Beneitez, Gijs W. E. Santen, Quinten Waisfisz, Mariet Elting, Frans J. W. Smiers, Anne J. de Pagter, Jean-Louis H. Kerkhoffs, Cornelis L. Harteveld, Maria del Mar Mañú-Pereira |
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| Přispěvatelé: | Institut Català de la Salut, [Rizzuto V] Recerca translacional en càncer en la infància i l’adolescència– Rare Anemia Disorders Research Laboratory, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. ERN-EuroBloodNet Member, Barcelona, Spain. Josep Carreras Leukaemia Research Institute, Badalona, Spain. Department of Medicine, Universitat de Barcelona, Barcelona, Spain. [Koopmann TT] Department of Clinical Genetics, Leiden University Medical Center, ERN-EuroBloodNet Member, Leiden, Netherlands. [Blanco-Álvarez A, Tazón-Vega B] Hematologic Molecular Genetics Unit, Hematology Department, Hospital Universitari Vall d’Hebron, ERN-EuroBloodNet Member, Barcelona, Spain. [Idrizovic A, Mañú-Pereira MDM] Recerca translacional en càncer en la infància i l’adolescència– Rare Anemia Disorders Research Laboratory, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. ERN-EuroBloodNet Member, Barcelona, Spain. [Díaz de Heredia C, Velasco P] Servei d’Oncologia i Hematologia Pediàtriques, Vall d’Hebron Hospital Universitari, Barcelona, Spain. ERN-EuroBloodNet Member, Barcelona, Spain. [Beneitez D] Unitat de Trastorns dels glòbuls vermells, Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. ERN-EuroBloodNet Member, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Human genetics, Amsterdam Reproduction & Development (AR&D) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pediatrics
medicine.medical_specialty Blood transfusion técnicas de investigación::técnicas genéticas::análisis de secuencias::análisis de secuencias de ADN [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Anemia Physiology medicine.medical_treatment Dominant beta-thalassemia enfermedades hematológicas y linfáticas::enfermedades hematológicas::anemia::anemia hemolítica::anemia hemolítica congénita::talasemia::talasemia beta [ENFERMEDADES] lcsh:Physiology whole exome sequencing 03 medical and health sciences 0302 clinical medicine Targeted ngs Seqüències d'inserció de l'ADN Physiology (medical) medicine unstable hemoglobinopathies Exome sequencing 030304 developmental biology Original Research next generation sequencing 0303 health sciences Hb Debrousse enfermedades hematológicas y linfáticas::enfermedades hematológicas::hemoglobinopatías [ENFERMEDADES] lcsh:QP1-981 business.industry Hemoglobinopatia medicine.disease Hemolysis Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis DNA [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] 3. Good health Hemic and Lymphatic Diseases::Hematologic Diseases::Hemoglobinopathies [DISEASES] Chronic hemolytic anemia Talassèmia 030220 oncology & carcinogenesis dominant beta-thalassemia business rare anemia disorders Hemic and Lymphatic Diseases::Hematologic Diseases::Anemia::Anemia Hemolytic::Anemia Hemolytic Congenital::Thalassemia::beta-Thalassemia [DISEASES] |
| Zdroj: | Scientia Frontiers in Physiology, 12. FRONTIERS MEDIA SA Frontiers in Physiology Frontiers in Physiology, Vol 12 (2021) Rizzuto, V, Koopmann, T T, Blanco-Álvarez, A, Tazón-Vega, B, Idrizovic, A, Díaz de Heredia, C, del Orbe, R, Pampliega, M V, Velasco, P, Beneitez, D, Santen, G W E, Waisfisz, Q, Elting, M, Smiers, F J W, de Pagter, A J, Kerkhoffs, J-L H, Harteveld, C L & Mañú-Pereira, M D M 2021, ' Usefulness of NGS for Diagnosis of Dominant Beta-Thalassemia and Unstable Hemoglobinopathies in Five Clinical Cases ', Frontiers in Physiology, vol. 12, 628236 . https://doi.org/10.3389/fphys.2021.628236 Frontiers in Physiology, 12:628236. Frontiers Research Topics |
| ISSN: | 1664-042X |
| DOI: | 10.3389/fphys.2021.628236 |
| Popis: | Seqüenciació de nova generació; Trastorns d’anèmia rars; Hemoglobinopaties inestables Next generation sequencing; Rare anemia disorders; Unstable hemoglobinopathies Secuenciación de nueva generación; Trastornos raros de la anemia; Hemoglobinopatías inestables Unstable hemoglobinopathies (UHs) are rare anemia disorders (RADs) characterized by abnormal hemoglobin (Hb) variants with decreased stability. UHs are therefore easily precipitating, causing hemolysis and, in some cases, leading to dominant beta-thalassemia (dBTHAL). The clinical picture of UHs is highly heterogeneous, inheritance pattern is dominant, instead of recessive as in more prevalent major Hb syndromes, and may occur de novo. Most cases of UHs are not detected by conventional testing, therefore diagnosis requires a high index of suspicion of the treating physician. Here, we highlight the importance of next generation sequencing (NGS) methodologies for the diagnosis of patients with dBTHAL and other less severe UH variants. We present five unrelated clinical cases referred with chronic hemolytic anemia, three of them with severe blood transfusion dependent anemia. Targeted NGS analysis was performed in three cases while whole exome sequencing (WES) analysis was performed in two cases. Five different UH variants were identified correlating with patients’ clinical manifestations. Four variants were related to the beta-globin gene (Hb Bristol—Alesha, Hb Debrousse, Hb Zunyi, and the novel Hb Mokum) meanwhile one case was caused by a mutation in the alpha-globin gene leading to Hb Evans. Inclusion of alpha and beta-globin genes in routine NGS approaches for RADs has to be considered to improve diagnosis’ efficiency of RAD due to UHs. Reducing misdiagnoses and underdiagnoses of UH variants, especially of the severe forms leading to dBTHAL would also facilitate the early start of intensive or curative treatments for these patients. This study was supported by funding from the authors’ institutions and the European Commission H2020-MSCA-ITN-2019, Grant Agreement N860436, “EVIDENCE.” |
| Databáze: | OpenAIRE |
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