Open AccessGermline RUNX1 variants in paediatric patients in a French specialised centre
Author(s) -
Liu Cécile,
Ballerini Paola,
Nguyen Guillaume,
Mincheva Zoia,
Copin Bruno,
Bouslama Boutheina,
Leverger Guy,
Petit Arnaud,
Favier Rémi,
Lapillonne Hélène,
Boutroux Hélène
Publication year - 2023
Publication title -
ejhaem
Language(s) - English
Resource type - Journals
ISSN - 2688-6146
DOI - 10.1002/jha2.594
Subject(s) - germline , runx1 , malignancy , germline mutation , family history , phenotype , disease , medicine , biology , genetics , mutation , pathology , haematopoiesis , gene , stem cell
Abstract Familial platelet disorder with associated myeloid malignancy (FPD‐MM; OMIM 601399) is related to germline RUNX1 mutation. The pathogenicity of RUNX1 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 RUNX1 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 RUNX1 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 RUNX1 suggest the implication of germline variants in the onset of the malignancy.