LAUSR

Dear Editor, Hereditary thrombocythemia is a very rare autosomal dominant disorder associated with polyclonal hematopoiesis of the megakaryocytic lineage [1, 2]. Thrombocythemia 1 (THCYT1), caused by THPO variant, has been reported in Dutch [3, 4], Japanese [5, 6], Polish [7], Italian [1], Filipino [2], and German [8] families. Here, we report the first case of a Korean boy diagnosed as having THCYT1 using next-generation sequencing (Table 1). This study was approved by the Institutional Review Board of Keimyung University Dongsan Hospital, Daegu, Korea (approval number: 2019-01-015-002). Informed consent was obtained from all individuals in this study. In September 2017, a 25-day-old male infant was transferred to Keimyung University Dong San Hospital, following an incidental finding of an abnormal white blood cell (WBC) count. He had congenital defects of his left hand (Fig. 1A and 1B). One of his two sisters had a history of persistent thrombocythemia of unknown etiology from the age of five months, which was diagnosed at another hospital. His parents and another sister had no past medical history. Laboratory examination at admission showed a WBC count of 34.6×10/L. His hemoglobin level was 134 g/L, and the platelet count was 197×10/L. The WBC count, determined by manual differential cell count, gradually increased to 57.61×10/L with 3% blasts, 45% segmented cells, 32% lymphocytes, 10% monocytes, 5% eosinophils, and 1% basophils at 39 days of age. Bone marrow analysis at 42 days old showed an increase in the myeloid series with some myeloblasts (5.1%). Megakaryocytes were adequate in number and morphologically normal. We initially suspected juvenile myelomonocytic leukemia; however, clinical and genetic evaluations were inadequate to confirm this diagnosis. At four months of age, the leukocytosis resolved spontaneously; however, the platelet count increased to >1,000×10/L and was sustained at this level (Fig. 1C). There was no evidence of infection, tissue damage, allergic disease, or autoimmune inflammation associated with secondary thrombocythemia. A second bone marrow analysis revealed slightly increased cellularity with an adequate myeloid:erythroid ratio (2.38:1) and no abnormal finding except for increased megakaryocytes (Fig. 1D). Genetic evaluation for essential thrombocythemia was performed for JAK2, JAK2 V617F, MPL, and CALR, and no pathogenic variant was observed. Treatment with low-dose acetyl salicylic acid (3 mg/kg) was initiated at four months of age. Targeted exome sequencing was performed to determine the genetic cause of the thrombocythemia in the absence of JAK2/ MPL/CALR mutation. Library preparation was performed using