Usefulness of NGS for Diagnosis of Dominant Beta-Thalassemia and Unstable Hemoglobinopathies in Five Clinical Cases.

Autor:	Rizzuto V; Translational Research in Child and Adolescent Cancer - Rare Anemia Disorders Research Laboratory, Vall d'Hebron Research Institute, 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; Hematologic Molecular Genetics Unit, Hematology Department, Hospital Universitari Vall d'Hebron, ERN-EuroBloodNet Member, Barcelona, Spain., Tazón-Vega B; Hematologic Molecular Genetics Unit, Hematology Department, Hospital Universitari Vall d'Hebron, ERN-EuroBloodNet Member, Barcelona, Spain., Idrizovic A; Translational Research in Child and Adolescent Cancer - Rare Anemia Disorders Research Laboratory, Vall d'Hebron Research Institute, ERN-EuroBloodNet Member, Barcelona, Spain., Díaz de Heredia C; Oncohematologic Pediatrics Department, Hospital Universitari Vall d'Hebron, ERN-EuroBloodNet Member, Barcelona, Spain., Del Orbe R; Hematology Department, Hospital Universitario Cruces, Barakaldo, Spain., Pampliega MV; Hematology Department, Hospital Universitario Cruces, Barakaldo, Spain., Velasco P; Oncohematologic Pediatrics Department, Hospital Universitari Vall d'Hebron, ERN-EuroBloodNet Member, Barcelona, Spain., Beneitez D; Red Blood Cell Disorders Unit, Hematology Department, Hospital Universitari Vall d'Hebron, ERN-EuroBloodNet Member, Barcelona, Spain., Santen GWE; Department of Clinical Genetics, Leiden University Medical Center, ERN-EuroBloodNet Member, Leiden, Netherlands., Waisfisz Q; Department of Clinical Genetics, VU Medical Center, Amsterdam, Netherlands., Elting M; Department of Clinical Genetics, VU Medical Center, Amsterdam, Netherlands., Smiers FJW; Department of Pediatric Hematology, Leiden University Medical Center, Leiden, Netherlands., de Pagter AJ; Department of Pediatric Hematology, Leiden University Medical Center, Leiden, Netherlands., Kerkhoffs JH; Department of Hematology, HAGA City Hospital, The Hague, Netherlands., Harteveld CL; Department of Clinical Genetics, Leiden University Medical Center, ERN-EuroBloodNet Member, Leiden, Netherlands., Mañú-Pereira MDM; Translational Research in Child and Adolescent Cancer - Rare Anemia Disorders Research Laboratory, Vall d'Hebron Research Institute, ERN-EuroBloodNet Member, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in physiology [Front Physiol] 2021 Feb 05; Vol. 12, pp. 628236. Date of Electronic Publication: 2021 Feb 05 (Print Publication: 2021).
DOI:	10.3389/fphys.2021.628236
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Rizzuto, Koopmann, Blanco-Álvarez, Tazón-Vega, Idrizovic, Díaz de Heredia, Del Orbe, Pampliega, Velasco, Beneitez, Santen, Waisfisz, Elting, Smiers, de Pagter, Kerkhoffs, Harteveld and Mañú-Pereira.)
Databáze:	MEDLINE
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