ASH 2021 | Germline predispositions in early onset MDS

Myelodysplastic syndromes (MDS) are rare in younger patients. It is therefore of interest to investigate potential germline predispositions in patients under the age of 60 who present with non-therapy related MDS. Valeria Santini, MD, University of Florence, Florence, Italy, discusses an analysis of 21 MDS cases with an age at diagnosis of under 60 years and anemia. After morphological confirmation of dysplasia suggestive of MDS, whole exome sequencing (WES) was carried out on bone marrow DNA or peripheral blood DNA, as well as targeted next-generation sequencing on DNA extracted from saliva to provide a germline confirmation. Analysis revealed that 5 cases carried variants suspected responsible of red blood cell (RBC) membrane defects in both bone marrow/peripheral blood DNA and saliva DNA, including PIEZ01. A significant difference in osmolarity curves indicated the pathogenic role of the identified variants. These findings suggest that co-existence of inherited RBC membrane defects with MDS may determine earlier clinical manifestation. Prof. Santini comments on the importance of detailed investigation when faced with a case of de novo MDS at an unusually young age. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.