Usefulness of NGS for Diagnosis of Dominant Beta-Thalassemia and Unstable Hemoglobinopathies in Five Clinical Cases
Rizzuto, Valeria (Universitat de Barcelona. Departament de Medicina)
Koopmann, Tamara T. (Leiden University Medical Center)
Blanco, Adoración (Hospital Universitari Vall d'Hebron)
Tazón-Vega, Bárbara (Hospital Universitari Vall d'Hebron)
Idrizovic, Amira (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Díaz de Heredia, Cristina (Hospital Universitari Vall d'Hebron)
Del Orbe Barreto, Rafael Andrés (Hospital Universitario de Cruces (Barakaldo, País Basc))
Pampliega, Miriam Vara (Hospital Universitario de Cruces (Barakaldo, País Basc))
Velasco, Pablo (Hospital Universitari Vall d'Hebron)
Beneitez Pastor, David (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Santen, Gijs Santen W.E. (Leiden University Medical Center)
Waisfisz, Quinten (VU Medical Center)
Elting, Mariet (VU Medical Center)
Smiers, Frans J.W. (Leiden University Medical Center)
de Pagter, Anne J. (Leiden University Medical Center)
Kerkhoffs, Jean Louis H. (AGA City Hospital)
Harteveld, Cornelis L. (Leiden University Medical Center)
Mañú Pereira, María del Mar (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras

Date:	2021
Abstract:	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.
Grants:	European Commission. Horizon 2020 860436
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Frontiers in physiology, Vol. 12 (may 2021) , p. 628236, ISSN 1664-042X

DOI: 10.3389/fphys.2021.628236
PMID: 33613322

9 p, 1.4 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
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