POLE codes for DNA polymerase epsilon (Pol ε) and variants of Pol ε catalytic subunit 1 can be pathogenic. We recently reported a novel POLE gene variant (p.[D1131fs];[T1891del]) which leads to bone marrow failure in two Japanese sisters. Here, we describe the successful course of hematopoietic stem cell transplantation of these two sisters. Both cases were born with congenital anemia and remained transfusion dependent. Their bone marrow showed gradually proceeding trilineage dysplasia. They both underwent HCT from an unrelated bone marrow donor and successfully achieved engraftment. Ten and eight years have passed respectively, and they are doing well without transfusion.

Bernard-Soulier syndrome (BSS) is caused by defects in GP1BA, GP1BB, or GP9 genes. Patients with 22q11.2 deletion syndrome (22q11.2DS) are obligate carriers for BSS because GP1BB resides on chromosome 22q11.2. A 15-month-old girl without bleeding symptoms had giant platelets and thrombocytopenia. Physical findings and macrothrombocytopenia suggested 22q11.2DS, which was confirmed by fluorescence in situ hybridization. Flow-cytometry showed decreased GPIbα on the platelets. A novel variant in GP1BB, p.(Val169_Leu172del), was revealed by gene panel testing. These findings confirmed that she had BSS. This case suggests that any 22q11.2DS patient associated with macrothrombocytopenia should be further investigated for the presence of BSS.

Takenouchi-Kosaki syndrome (TKS) exhibits clinical features represented by macrothrombocytopenia, developmental delay, dysmorphic facial features, and deafness. There is little information on the treatment for macrothrombocytopenia in TKS. Splenectomy has been a contraindication for inherited thrombocytopenia. In the case of autoimmune haemolytic anaemia (AIHA) with TKS that we previously reported, AIHA initially resolved with prednisolone; however, it gradually became resistant to drug therapy. We performed splenectomy, and post-operatively, both anaemia and macrothrombocytopenia improved. This is a novel effect of splenectomy for thrombocytopenia in TKS, which suggests that splenectomy could be a treatment option for thrombocytopenia in TKS.