MYH9‐related disease: Assessment of the pathogenicity of a new mutation

A 19-year-old woman was addressed to the Haemophilia Treatment Center in august 2022 due thrombocytopenia on complete blood count (CBC). Medical examination did not reveal any signs of bleeding a daily basis, and she experienced appendectomy avulsion deciduous teeth without bleeding. ISTH assessment tool 0. There no family history or thrombocytopenia. CBC performed laboratory XN10 analyzer (Sysmex) disclosed thrombocytopenia, (66 × 109·L−1) by fluorocytometry. Mean platelet volume assessable anisocytosis. Furthermore, immature fraction dramatically increased at 47.7%. Routine coagulation tests (PT, APTT, fibrinogen activity) were normal, there von Willebrand Factor deficiency. Platelet aggregation assay revealed abnormality. Glycoprotein receptors GpIb GpIIbIIIa present (GpIb 30800 46437 per platelet, normal values respectively 27000–49000 37000–65000). Other common causes excluded: antibodies detection flow cytometry monoclonal antibody immobilized antigen (MAIPA kit, apDia) negative, thyroid stimulating hormone antinuclear viral serologies for Hepatitis B virus, C virus human immunodeficiency lupus anticoagulant. Examination peripheral smear showed abnormal neutrophils with typical Döhle-like inclusions almost 100% (Figure 1A). strong platelets anisocytosis observed presence macroplatelets giant 1B). Immunofluorecence labelling non-muscle myosin heavy chain IIA (NMHC-IIA) protein small aggregates granulocytes compared control 1C,D). To confirm diagnosis, we gene test MYH9-related disease. Sequencing analysis novel c.3131_3151dup p.(Gln1044_Arg1050dup) duplication exon 25 MYH9 gene. This sequence variation found her parents (the true paternity confirmed) siblings who all had 2) confirming de novo status this variation. The mutation functional study immunofluorescence are two arguments classify new as probably pathogenic according American College Genetics Genomics classification (ACMG 4) [1]. disease is rare illness involving multiple organs such ear, eyes, kidneys, liver cells [2]. At time patient renal function hearing sight loss. Mutations can lead modification structure helical tail lower risk extra hematological manifestations than variants affecting globular head [3]. Indeed, resulting modifications terminal part non-helical normally associated isolated macrothrombocytopenia Thrombocytopenia also less severe amino acid [4]. syndrome leading cause macrothrombocytopenia. confirmed pathognomonic sign disorder [5]. However, these inclusion bodies constant. Thus, case macrothrombocytopenia, genetic essential avoid misdiagnosing delaying patient's management. Antoine Babuty, Pierre Boisseau Marion Eveillard research. Boisseau, Nicolas Drillaud, Marc Fouassier wrote paper. authors have conflict interest declare. research received specific grant from funding agency public, commercial not-for-profit sectors. According French regulations, oral consent obtained. data that support findings available corresponding author upon reasonable request.