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

Autor: 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
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: HemaSphere, Vol 5, Iss 4, p e539 (2021)
Druh dokumentu: article
ISSN: 2572-9241
00000000
DOI: 10.1097/HS9.0000000000000539
Popis: 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.
Databáze: Directory of Open Access Journals
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