Figure 1

H&E staining of the bone marrow, Pedigree, AK2 gene and protein structure. (A) H&E staining of the bone marrow. Control; bone marrow from an age-matched individual showing adequate cellularity with all normal hemopoietic cell lines represented and without predominance of any particular lineage. Pre-Tx; pre-transplant bone marrow biopsy from the patient at 13 months of age before bone marrow transplant showing myeloid maturation only through the promyelocyte/myelocyte stage. Only occasional neutrophils were seen. Post-Tx; post-transplant bone marrow biopsy from affected patient after bone marrow transplant showing normocellular bone marrow with trilineage hematopoiesis (all images at 100X). (B) Pedigree of the family identified with mutations in the AK2 gene. Both parents and siblings are unaffected and heterozygous for the mutation while the patient is homozygous. Ages are representative of the individual ages at the time of manuscript submission. Asterisk denotes the age of the patient when he died following bone marrow transplant complication. (C) Structure of the AK2 gene (GenBank: NM_001625), location of the Ser208Pro mutation relative to the polypeptide stretch, and homology alignment of the AK2 β-strands IV (L125-I129) and VII (G206-A212) regions. The secondary structure assignments are according to the human AK2 crystal structure atomic coordinates, PDB 2C9Y, highlighted in pink boxes. Residues in bold capital letters are invariants in all species examined, only 13 are shown. Residues in capital letters (not bold) are highly conserved, and residues in small letters seem dispensable. Highlighted in green is the Ser208 position. (D) Ribbon representation of the AK2 protein 3D structure, PDB 2C9Y, with the position of Ser208 depicted (replaced with a Pro in the patient of this study), plus the position of other previously reported mutations in the AK2 protein. BATP (letters in yellow) is the ATP binding domain.