Journal
INTERNATIONAL JOURNAL OF HEMATOLOGY
Volume 118, Issue 3, Pages 400-405Publisher
SPRINGER JAPAN KK
DOI: 10.1007/s12185-023-03575-1
Keywords
Familial platelet disorder; Myelodysplastic syndrome; Acute myeloid leukemia; RUNX1 mutation; Germline; Genetic pedigree
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This study presents two pedigrees, one diagnosed with familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) molecularly and another highly suspected. Both pedigrees showed a family history of thrombocytopenia, platelet dysfunction, and hematological malignancies, highlighting the importance of searching for gene mutations associated with germline predisposition.
Germline mutations in RUNX1 result in rare autosomal-dominant familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). As genetic analysis is becoming increasingly prevalent, the diagnosis rate of FPD/AML is expected to increase. In this report, we present two pedigrees, one diagnosed molecularly and another highly suspected to be FPD/AML, whose members both received allogeneic hematopoietic stem cell transplantation (HSCT). Both pedigrees had a family history of thrombocytopenia, platelet dysfunction, and hematological malignancies. One family inherited a frameshift mutation (p.P240fs) of RUNX1, a known pathogenic variant. Another family inherited a point mutation (p.G168R) in the runt-homology domain, the clinical significance of which is uncertain at this point. As this mutation was completely absent from all population databases and had a relatively high REVEL score of 0.947, we thought that it would be dangerous to ignore its possible pathogenicity. Consequently, we avoided choosing HSCT donors from relatives of both families and performed HSCT from unrelated donors. In conclusion, our experience with two families of FPD/AML highlights the importance of searching for gene mutations associated with germline predisposition and indicates the necessity of developing a donor coordination system for FPD/AML patients, as well as a support system for families.
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