Background- inherited bone marrow failure syndromes (IBMFS) are a group of genetic disorders characterized by inadequate blood cells production. IBMFS may be manifested as an isolated cytopenia (i.e. anemia, neutropenia or thrombocytopenia) or as pancytopenia. Other organ systems are often affected. Most IBMFS, pose increased risk for malignant transformation, including myelodysplastic syndromes, acute leukemia and solid tumors. The diagnosis of these syndromes is complicated by a large phenotypic variability and an increasing number of mutated genes implicated in each disorder.
Aim of the study - to improve the genetic diagnosis of children with IBMFS by using gene capture and next generation sequencing (NGS). Our goal is that NGS will become the first line genetic diagnostic tool for all patients diagnosed with bone marrow failure syndromes.
Methods- Patients with clinical and laboratory characteristics of IBMFS (included in the Israeli bone marrow failure registry), in whom no genetic diagnosis was achieved by a gene-by-gene sequencing approach were included in the study., Gene capture of roughly 200 genes known to be involved in IBMFS, followed by NGS was performed on these patients.
Results – out of 40 evaluated patients, mutated genes were found in 13 (33%). Among these, in 3 cases, the diagnosis was different than that suspected. The remaining 10 were genetically diagnosed in an accurate, timely, and cost effective manner.
Conclusions - Our results support the advantages of integration of a broad, unbiased genetic screening into the diagnostic workup of IBMFS in children and young adults
