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Targeted Next Generation Sequencing and Diagnosis of Congenital Hemolytic Anemias: A Three Years Experience Monocentric Study

Congenital hemolytic anemias (CHAs) are heterogeneous and rare disorders caused by alterations in structure, membrane transport, metabolism, or red blood cell production. The pathophysiology of these diseases, in particular the rarest, is often poorly understood, and easy-to-apply tools for diagnosi...

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Autores principales: Fermo, Elisa, Vercellati, Cristina, Marcello, Anna Paola, Keskin, Ebru Yilmaz, Perrotta, Silverio, Zaninoni, Anna, Brancaleoni, Valentina, Zanella, Alberto, Giannotta, Juri A., Barcellini, Wilma, Bianchi, Paola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176228/
https://www.ncbi.nlm.nih.gov/pubmed/34093240
http://dx.doi.org/10.3389/fphys.2021.684569
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author Fermo, Elisa
Vercellati, Cristina
Marcello, Anna Paola
Keskin, Ebru Yilmaz
Perrotta, Silverio
Zaninoni, Anna
Brancaleoni, Valentina
Zanella, Alberto
Giannotta, Juri A.
Barcellini, Wilma
Bianchi, Paola
author_facet Fermo, Elisa
Vercellati, Cristina
Marcello, Anna Paola
Keskin, Ebru Yilmaz
Perrotta, Silverio
Zaninoni, Anna
Brancaleoni, Valentina
Zanella, Alberto
Giannotta, Juri A.
Barcellini, Wilma
Bianchi, Paola
author_sort Fermo, Elisa
collection PubMed
description Congenital hemolytic anemias (CHAs) are heterogeneous and rare disorders caused by alterations in structure, membrane transport, metabolism, or red blood cell production. The pathophysiology of these diseases, in particular the rarest, is often poorly understood, and easy-to-apply tools for diagnosis, clinical management, and patient stratification are still lacking. We report the 3-years monocentric experience with a 43 genes targeted Next Generation Sequencing (t-NGS) panel in diagnosis of CHAs; 122 patients from 105 unrelated families were investigated and the results compared with conventional laboratory pathway. Patients were divided in two groups: 1) cases diagnosed with hematologic investigations to be confirmed at molecular level, and 2) patients with unexplained anemia after extensive hematologic investigation. The overall sensitivity of t-NGS was 74 and 35% for families of groups 1 and 2, respectively. Inside this cohort of patients we identified 26 new pathogenic variants confirmed by functional evidence. The implementation of laboratory work-up with t-NGS increased the number of diagnoses in cases with unexplained anemia; cytoskeleton defects are well detected by conventional tools, deserving t-NGS to atypical cases; the diagnosis of Gardos channelopathy, some enzyme deficiencies, familial siterosterolemia, X-linked defects in females and other rare and ultra-rare diseases definitely benefits of t-NGS approaches.
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spelling pubmed-81762282021-06-05 Targeted Next Generation Sequencing and Diagnosis of Congenital Hemolytic Anemias: A Three Years Experience Monocentric Study Fermo, Elisa Vercellati, Cristina Marcello, Anna Paola Keskin, Ebru Yilmaz Perrotta, Silverio Zaninoni, Anna Brancaleoni, Valentina Zanella, Alberto Giannotta, Juri A. Barcellini, Wilma Bianchi, Paola Front Physiol Physiology Congenital hemolytic anemias (CHAs) are heterogeneous and rare disorders caused by alterations in structure, membrane transport, metabolism, or red blood cell production. The pathophysiology of these diseases, in particular the rarest, is often poorly understood, and easy-to-apply tools for diagnosis, clinical management, and patient stratification are still lacking. We report the 3-years monocentric experience with a 43 genes targeted Next Generation Sequencing (t-NGS) panel in diagnosis of CHAs; 122 patients from 105 unrelated families were investigated and the results compared with conventional laboratory pathway. Patients were divided in two groups: 1) cases diagnosed with hematologic investigations to be confirmed at molecular level, and 2) patients with unexplained anemia after extensive hematologic investigation. The overall sensitivity of t-NGS was 74 and 35% for families of groups 1 and 2, respectively. Inside this cohort of patients we identified 26 new pathogenic variants confirmed by functional evidence. The implementation of laboratory work-up with t-NGS increased the number of diagnoses in cases with unexplained anemia; cytoskeleton defects are well detected by conventional tools, deserving t-NGS to atypical cases; the diagnosis of Gardos channelopathy, some enzyme deficiencies, familial siterosterolemia, X-linked defects in females and other rare and ultra-rare diseases definitely benefits of t-NGS approaches. Frontiers Media S.A. 2021-05-21 /pmc/articles/PMC8176228/ /pubmed/34093240 http://dx.doi.org/10.3389/fphys.2021.684569 Text en Copyright © 2021 Fermo, Vercellati, Marcello, Keskin, Perrotta, Zaninoni, Brancaleoni, Zanella, Giannotta, Barcellini and Bianchi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Fermo, Elisa
Vercellati, Cristina
Marcello, Anna Paola
Keskin, Ebru Yilmaz
Perrotta, Silverio
Zaninoni, Anna
Brancaleoni, Valentina
Zanella, Alberto
Giannotta, Juri A.
Barcellini, Wilma
Bianchi, Paola
Targeted Next Generation Sequencing and Diagnosis of Congenital Hemolytic Anemias: A Three Years Experience Monocentric Study
title Targeted Next Generation Sequencing and Diagnosis of Congenital Hemolytic Anemias: A Three Years Experience Monocentric Study
title_full Targeted Next Generation Sequencing and Diagnosis of Congenital Hemolytic Anemias: A Three Years Experience Monocentric Study
title_fullStr Targeted Next Generation Sequencing and Diagnosis of Congenital Hemolytic Anemias: A Three Years Experience Monocentric Study
title_full_unstemmed Targeted Next Generation Sequencing and Diagnosis of Congenital Hemolytic Anemias: A Three Years Experience Monocentric Study
title_short Targeted Next Generation Sequencing and Diagnosis of Congenital Hemolytic Anemias: A Three Years Experience Monocentric Study
title_sort targeted next generation sequencing and diagnosis of congenital hemolytic anemias: a three years experience monocentric study
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176228/
https://www.ncbi.nlm.nih.gov/pubmed/34093240
http://dx.doi.org/10.3389/fphys.2021.684569
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