Germline RUNX1 variants in paediatric patients in a French specialised centre.

Familial platelet disorder with associated myeloid malignancy (FPD-MM; OMIM 601399) is related to germline mutation. The pathogenicity of variants was initially linked to FPD-MM phenotype, but the discovery of new variants through the expansion of genetic explorations in leukaemia is questioning this assertion. In this study, we add 10 families with germline variant explored at Armand Trousseau Hospital for leukaemia diagnosis or thrombocytopenia, to the 259 described so far. Detailed description of their personal and family history of haematological pathologies allows identifying three phenotypes related to germline variants: thrombocytopenia and/or malignant haematological disease with family history of haematological diseases, thrombocytopenia with no family history of haematological diseases and acute lymphoblastic leukaemia (ALL) with no family history of haematological diseases. In the latter phenotype, ALL characteristics involving suggest the implication of germline variants in the onset of the malignancy.