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Next-generation Sequencing in Bone Marrow Failure Syndromes and Isolated Cytopenias: Experience of the Spanish Network on Bone Marrow Failure Syndromes

Authors :
Eva Gálvez
Elena Vallespín
Elena G. Arias-Salgado
Carmen Sánchez-Valdepeñas
Yari Giménez
Susana Navarro
Paula Río
Massimo Bogliolo
Roser Pujol
Montserrat Peiró
Julián Nevado
Josune Zubicaray
Elena Sebastián
Albert Catalá
Cristina Beléndez
Cristina Díaz de Heredia
Ana Galera
Isabel Badell
Luis Madero
Rosario Perona
Leandro Sastre
Jordi Surrallés
Juan Bueren
Pablo Lapunzina
Julián Sevilla
Source :
HemaSphere, Vol 5, Iss 4, p e539 (2021)
Publication Year :
2021
Publisher :
Wiley, 2021.

Abstract

Inherited bone marrow failure syndromes (IBMFSs) are a group of congenital rare diseases characterized by bone marrow failure, congenital anomalies, high genetic heterogeneity, and predisposition to cancer. Appropriate treatment and cancer surveillance ideally depend on the identification of the mutated gene. A next-generation sequencing (NGS) panel of genes could be 1 initial genetic screening test to be carried out in a comprehensive study of IBMFSs, allowing molecular detection in affected patients. We designed 2 NGS panels of IBMFS genes: version 1 included 129 genes and version 2 involved 145 genes. The cohort included a total of 204 patients with suspected IBMFSs without molecular diagnosis. Capture-based targeted sequencing covered > 99% of the target regions of 145 genes, with more than 20 independent reads. No differences were seen between the 2 versions of the panel. The NGS tool allowed a total of 91 patients to be diagnosed, with an overall molecular diagnostic rate of 44%. Among the 167 patients with classified IBMFSs, 81 patients (48%) were diagnosed. Unclassified IBMFSs involved a total of 37 patients, of whom 9 patients (24%) were diagnosed. The preexisting diagnosis of 6 clinically classified patients (6%) was amended, implying a change of therapy for some of them. Our NGS IBMFS gene panel assay is a useful tool in the molecular diagnosis of IBMFSs and a reasonable option as the first tier genetic test in these disorders.

Details

Language :
English
ISSN :
25729241 and 00000000
Volume :
5
Issue :
4
Database :
Directory of Open Access Journals
Journal :
HemaSphere
Publication Type :
Academic Journal
Accession number :
edsdoj.7171cad4d97c4e6b9d227d6066cf270c
Document Type :
article
Full Text :
https://doi.org/10.1097/HS9.0000000000000539