A new family with a germline ANKRD26 mutation and predisposition to myeloid malignancies

Recently a mother-daughter pair with life-long thrombocytopenia presented for consultation regarding their presumed diagnoses of autoimmune-based idiopathic thrombocytopenic purpura (ITP) and their extended family history of bleeding and myeloid malignancies (Figure 1A). The proband/mother (III:4) had been diagnosed with myelodysplastic syndrome (MDS), and the daughter (IV:3) was 32 weeks pregnant. A family history revealed 10 of 28 family members with thrombocytopenia, 4 of whom also had MDS/acute myeloid leukemia (AML). Consideration was given to known alleles associated with congenital thrombocytopenia with predisposition to MDS/AML. Among RUNX1, GATA2, and CEPBA, three genes in which germline mutations predispose to myeloid malignancies, only familial platelet disorder (FPD)/germline RUNX1 mutation is associated with thrombocytopenia and platelet dysfunction.1 Recently, however, mutations within the 5′ untranslated region (UTR) of ANKRD26 on chromosome 10p12 have been associated with Thrombocytopenia 2 (THC2), an autosomal-dominant congenital thrombocytopenia, and in one series a 30-fold increase in the frequency of MDS/AML. 2–5