Germline copy number variants in RUNX1: An updated case report and a decade-old red herring

TL;DR

A woman with a blood disorder and leukemia was found to have a RUNX1 gene deletion, showing the need for updated genetic testing to detect copy number variants.

Contribution

Highlights the importance of re-evaluating genetic cases with advanced CNV detection methods for accurate diagnosis.

Findings

A RUNX1 exon 5-6 deletion was identified in a patient previously misattributed to GATA2 variants.

The case underscores the limitations of older molecular techniques in detecting copy number variants.

Comprehensive genetic evaluation is crucial for diagnosing conditions like RUNX1-FPD.

Abstract

Pathogenic/likely pathogenic (P/LP) germline variants in RUNX1 cause familial platelet disorder with associated myeloid malignancies (FPDMM), also known as RUNX1-Familial Platelet Disorder (RUNX1-FPD, or FPD), a condition characterized by qualitative and quantitative platelet defects and predisposition to hematopoietic malignancies. Here, we present follow up to a case of a woman with acute myeloid leukemia and lifelong thrombocytopenia which had previously been attributed to presumptive pathogenic (P) GATA2 missense variants. However, re-evaluation with updated molecular technology sensitive for detection of copy number variants (CNVs) led to the identification of a P deletion of exons 5-6 in RUNX1, which had been undetected when examined at first presentation. This case highlights the importance of comprehensive molecular evaluation and careful variant interpretation, especially regarding CNVs.

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