Novel ETV6 variant in a pediatric patient: insights into thrombocytopenia, macrocytosis, and coagulation test abnormalities

ETV6, located on chromosome 12, is a transcriptional repressor vital for hematopoietic development, particularly in megakaryocyte maturation. Mutations in ETV6 are associated with various clinical presentations and hematologic disorders, including thrombocytopenia and acute lymphoblastic leukemia. This case report identifies a novel ETV6 mutation with rare clinical presentations that have not been previously reported in the literature, providing new insights into the genetic basis of the condition. We report a 17-month-old boy who presented with recurrent epistaxis. Family history indicated thrombocytopenia in the mother and brother. Initial evaluations revealed thrombocytopenia and transient coagulation abnormalities, including prolonged prothrombin time (PT) and partial thromboplastin time (PTT). The coagulation tests normalized after two months. At 6 years of age, the patient developed unilateral lymphadenopathy unresponsive to antibiotics, with a biopsy revealing reactive follicular hyperplasia and a normal bone marrow biopsy result. Despite receiving fresh frozen plasma for abnormal coagulation values, as well as corticosteroids and intravenous immunoglobulin, there was no improvement in the coagulation tests. The patient also exhibited macrocytosis, which persisted despite correction of vitamin B12 deficiency. Genetic testing through whole exome sequencing identified a heterozygous ETV6 mutation (c.1030T > A:p.Tyr344Asn) in both the patient and his mother. Normalization of coagulation tests was achieved three months later. The patient is currently under close hematologic follow-up with serial bone marrow aspirations, and hematopoietic stem cell transplantation will be considered only if progression to myelodysplastic syndrome or leukemia occurs. The new ETV6 variant and its clinical presentations emphasize the need for genetic screening in similar cases, particularly with a family history of hematological disorders, to facilitate early diagnosis and improve patient management strategies. Further research is necessary to explore the implications of ETV6 mutations in hematopoiesis.