More than just mild thrombocytopenia: Clinical clues in the diagnosis of germline predisposition to malignancy from a rare ETV6 variant

Abstract

Key clinical message: In the evaluation of patients with longstanding mild thrombocytopenia, emphasis on family history, genetic testing, and collaborative clinical and laboratory-based family studies can ensure proper diagnosis and monitoring for malignancies.

Abstract: We report the diagnostic approach to mild and non-specific thrombocytopenia with unclear genetic findings in two sisters. Genetic sequencing revealed a rare variant in ETS Variant Transcription Factor 6, which is associated with inherited thrombocytopenia with predisposition to hematologic malignancy. Familial studies provided sufficient evidence for a likely pathogenic classification.

Keywords: genetics; hematology; oncology; pediatrics and adolescent medicine; thrombocytopenia.

FIGURE 1

Sanger sequencing confirming the heterozygous ETV6 c.1085A>G variant analyzed by Mutation Surveyor. The upper panel shows reference sequence; the middle panel shows patient sequence; the lower panel shows the variant as a peak.

FIGURE 2

Pedigree showing the segregation of the ETV6 c.1085A>G variant within the extended family of the proband (patient B). WT, wild type gene confirmed by genetic testing. Arrow indicates proband.