Family pedigree and sequence analysis of the AML1 gene. (A) The family pedigree is shown. Half-filled symbols indicate thrombocytopenia; the closed symbol, the individual who developed CMMoL; and open figures, unaffected family members. The index patient is indicated by the arrow. (B) Genomic and protein AML1 sequence in healthy and affected individuals. A single nucleotide deletion (arrowhead) within 5 consecutive C's generates a frameshift at amino acid position 218 (underlined) and premature chain termination (^*). (C) Schematic representation of the wild-type and mutant truncated AML1 protein. The predicted protein includes an intact runt homology domain (RHD) (amino acids 50 to 177) but lacks a transactivation domain (TAD) (amino acids 243 to 371). The position of the Pro218fs-Ter225 mutation is indicated by the arrow.