Deleterious mutations in the RUNX 1 gene cause hereditary leukemia due to a rare syndrome called Familial platelet Disorder with Associated Myeloid Malignancy (FPDMM). We describe the characteristics of a family with FPDMM due to a novel RUNX 1 mutation (L472X), located in the most 3-prime end of the gene reported to date. Our 36-year - old proband presented with incidentally detected thrombocytopenia and a family history suggestive of FPDMM. Contrary to previously described families, affected members of our kindred express an eczematous phenotype, reportedly most severe in members who develop leukemia. Pedigree analysis shows that the L472X mutation tracks with thrombocyto penia, acute leukemia, and eczema. The L472X mutation produces a stably expressed RUNX 1 protein product with a corresponding decrease in wild type RUNX 1 expression. Our data supports the inclusion of eczema in the FPDMM phenotype and suggests the possibility that the RUNX 1 L472X mutant causes the type of dominant negative affect that is associated with an elevated risk of leukemia in FPDMM families .
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