Predicted amino acid changes and family trees of patients with MECOM mutations. (A) Graphical representation of MECOM/EVI1 predicted protein with its major functional domains (top part) including zinc finger in green, nuclear localization signal (NLS) and asparagine/glutamine (Asp/Glu)-rich region in gray, and C-terminal binding protein (CTBP) binding in blue. The bottom part shows amino acid alignments using ClustalW, representing conservation among different species. (B) Three-dimensional (3D) model of the localization of amino acid substitutions (yellow part, indicated by an arrow), highlighting the proximity of these amino acids with DNA (purple/blue double helix). The structure representations originate from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB; www.rcsb.org/pdb) after BLAST alignment of MECOM variant proteins. (C) Family trees for the 6 patients with MECOM mutations. All mutations were de novo where parental DNA was available and both paternity and maternity were confirmed (families 4 to 6). In family 3, MECOM mutation was not identified in mother DNA, whereas paternal DNA was not available. See clinical details in Table 2. Bt, Bos taurus; Dr, Danio rerio; Gg, Gallus gallus; Hs, Homo sapiens; Mm, Mus musculus; Pt, Pan troglodytes; Rn, Rattus norvegicus; WT, wild-type.