Identification of Genetic Variants Using Next-Generation Sequencing in Pediatric Myelodysplastic Syndrome: From Disease Biology to Clinical Applications.

This study aimed to identify genetic variants using a customized next-generation sequencing (NGS) panel for pediatric myelodysplastic syndrome (pMDS) and to explore their associations with cytogenetic and clinical characteristics. Cytogenetic analyses were conducted using G-banding and fluorescence in situ hybridization. NGS was performed with the Ion Torrent Personal Genome Machine for the following genes: , , , , , , , , , , , , , , and . Analyses were performed with Ion Reporter 5.20.8.0 software. Genetic variants were classified using the dbSNP, 1000 Genomes, COSMIC, and Varsome databases. We analyzed 25 cases of pMDS; 15 presented abnormal karyotypes, and 19 showed genetic variants. Among the 29 variants identified across 12/15 genes, 27% were pathogenic and 14% were likely pathogenic, with and most frequently associated with disease progression. A new somatic variant of uncertain significance in was detected in seven patients showing heterogeneous clinical outcomes. Genetic variants were found in 7/10 patients with normal karyotypes, indicating that submicroscopic alterations can shed light on disease biology. Our results highlight the critical role of a targeted NGS panel in identifying molecular alterations associated with pMDS pathogenesis, thereby enhancing diagnostic precision, prognosis, and aiding in treatment selection.