is a rare disorder in children. It mostly occurs secondary to disorders such as malignancy, vitamin D deficiency, autoimmunity, and infections. 1,2 Primary MF has been reported in a limited number of children. [3][4][5] Germline mutations in genes such as MPL, VPS45, and RBSN are associated with primary MF. 6-8 A recent report described an Arab family with MF associated with a homozygous mutation in MPIG6B (also known as G6B or C6orf25). 9Another report described four unrelated Arab families with homozygous loss-of-function variants in MPIG6B associated with childhood MF. 10 MPIG6B is located in the class III region of the major histocompatibility complex and encodes G6B protein that interacts with protein tyrosine phosphatases Shp1 and Shp2. 11,12 G6B is primarily expressed in platelets. [13][14][15] G6B knockout mice had low platelet count, increased platelet volume, and platelet dysfunction. 10,16 We report two unrelated patients who presented during infancy with anemia, thrombocytopenia, and focal MF and had homozygous mutations in MPIG6B. The first case is a 10-year-old female who presented at 7 months of age with epistaxis and had thrombocytopenia and anemia. Her parents are first cousins. Physical examination was unremarkable. Blood smear showed some giant platelets and anisopoikilocytosis with teardrop cells, schistocytes, elliptocytes, and spherocytes. Bone marrow (BM) at age 1 year was hypercellular with megakaryocyte clusters, as shown in Figure S1. BM was infiltrated with large cells with vesicular nuclei and prominent nucleoli and was surrounded by a mixture of small lymphocytes and eosinophils.The large cells were positive for CD10, CD20, CD45, and CD79a and negative for CD3, CD7, CD15, CD30, CD34, CD56, CD57, pan CK, desmin, and synaptophysin. The background cells were positive for CD15, CD45, MPO and negative for other markers. There was a mild increase in reticulin fibers. Follow-up BM studies showed subsequent fading of lymphocytic infiltration, dysplastic megakaryocytes, a slight reduction in erythropoiesis, and a marked increase in MF with no myelodysplasia (Figure S1). Cytogenetic analysis was normal.Chromosomal fragility test, vitamin D, vitamin B12, and folate levels were normal. The patient required intermittent platelet transfusion.There was no major bleeding. The spleen progressively increased in size with an increase in platelet transfusion requirements. Splenectomy led to transient improvement in platelet counts. Whole exome sequencing (WES) revealed a homozygous loss-of-function mutation in MPIG6B: c.523C>T (p.Arg175Ter). Recently, the patient started to

No abstract