Two novel families with RUNX1 variants indicate glycine 168 as a new mutational hotspot: Implications for FPD/AML diagnosis
Year: 2024
Type: article
Study design: Case Report
Abstract: Correct interpretation of the pathogenicity of germline RUNX1 variants is essential for FPD/AML diagnosis, clinical management and leukaemia surveillance. We report two families with clear FPD/AML phenotypic features harbouring missense variants at RHD critical residue Gly168. Although classified as of unknown significance (VUS) by RUNX1-specific curation guidelines, these variants should rather be considered likely pathogenic, as supported by computational tools, structural modelling and dysregulated platelet expression of RUNX1-targets, adding Gly168 among amino acids currently recognised as mutational hotspots. Our data could help reduce the number of variants classified as VUS, providing evidence for updating RUNX1 guidelines, thus improving FPD/AML diagnosis.
Source: British Journal of Haematology
DOI: 10.1111/bjh.19776
Institutions: Universidad de Buenos Aires, Institute for Medical Research, Policlinico San Matteo Fondazione, University of Bologna, Austral University, Fundación Instituto Leloir, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Diagnóstico e Investigaciones Metabólicas, University of Pavia
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4403236434