2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Somatic <em>RUNX1</em> Variants in Hematologic Malignancy: Could they be germline?

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In this study, the researchers aimed to investigate whether patients with a RUNX1 variant identified in their blood or bone marrow biopsy were referred to the genetics department to determine whether the variant was germline or somatic. The study was conducted using retrospective chart reviews of patients from January 2021 to January 2022. The patients were identified based on pathogenic or likely pathogenic variants in RUNX1 and allele frequency suggesting a germline variant. The charts were reviewed to gather risk factors for RUNX1 familial platelet disorder with associated myeloid malignancies (RUNX1-FPDMM), such as a history of eczema, family history of hematological malignancy, and platelet count.<br /><br />The results showed that none of the patients with pathogenic variants of RUNX1 were referred to genetics, and only one patient had a family history of hematological malignancy. The number of patients identified with clinical characteristics of RUNX1-FPDMM was less than expected. Additionally, it was difficult to determine certain characteristics, such as a history of prolonged bruising and/or bleeding, that suggest RUNX1-FPDMM. The researchers suggest that inadequate documentation by providers unfamiliar with RUNX1-FPDMM may have contributed to these findings.<br /><br />In conclusion, the study found that patients with somatic RUNX1 variants are under-referred to genetics for possible germline testing. The low rate of family history of hematologic malignancy indicates that RUNX1-FPDMM may be rare or have lower penetrance than expected. The researchers propose improved communication with hematology colleagues to enhance the detection of RUNX1-FPDMM.

Asset Subtitle

Presenting Author - Kelly Wang, B.S.; Co-Author - Michael J. Sweredoski, Ph.D.; Co-Author - Negar Ghahramani, Ph.D.; Co-Author - Amanda S. Freed, MD;

Meta Tag

Counseling

Genetic Testing

Co-Author Michael J. Sweredoski, Ph.D.

Co-Author Negar Ghahramani, Ph.D.

Co-Author Amanda S. Freed, MD

Presenting Author Kelly Wang, B.S.

Keywords

RUNX1 variant

genetics department

germline variant

somatic variant

pathogenic variant

RUNX1-FPDMM

family history

hematological malignancy

platelet count

prolonged bruising