Exploring a Unique <i>RUNX1</i> Germline Mutation with a Double Nucleotide Variant: Implications for Clinical Significance

Abstract

<b><i>Introduction:</i></b> Myeloid neoplasms with germline <i>RUNX1</i> mutation, an autosomal dominant disease characterized by thrombocytopenia and risk of hematologic malignancy, usually have a single nucleotide variant or insertions/deletions in <i>RUNX1</i>. Here, we present a patient with double nucleotide variant (DNV) in <i>RUNX1</i>. <b><i>Case Presentation:</i></b> The patient was a woman with progressive thrombocytopenia. She had a strong family history of thrombocytopenia and hematologic malignancies with a high fatality rate. We detected that genomic <i>RUNX1</i> had consecutive DNV (c.352G&gt;T and c.352-1 G&gt;C) at its splice site, resulting in a frameshift mutation in exon 5. She rapidly progressed to a high-risk myeloid neoplasm owing to a germline <i>RUNX1</i> mutation. Allogeneic transplantation successfully resulted in durable complete remission. <b><i>Conclusion:</i></b> To our knowledge, this is the first report of hereditary myeloid neoplasm carrying DNV in <i>RUNX1</i>. A family history of thrombocytopenia and the rapid malignant transformation suggests the potential pathogenic significance of the DNV.