Figure 1.

Pedigree, ASNA1 and pathogenic variants. A, Pedigree of the family. Squares and circles indicate males and females, respectively. The arrowhead indicates the proband. Upper right symbols indicate dilated cardiomyopathy, lower right symbols indicate ventricular septal defect, and lower left symbol indicates atrial septal defect. Genetic status is displayed below the symbols: wt, wild-type. B, Schematic overview of the ASNA1 gene (top) and corresponding protein (bottom). Boxes represent exons; connecting lines represent intervening introns. ^ indicates active site involved in catalysis, + indicates ATP binding sites, and * indicates zinc-binding sites. Rare variants identified in our family are displayed at the bottom of the diagram. C, Ortholog alignment of ASNA1 (derived from Ensembl reference sequences), showing high degree of protein conservation across vertebrates. Positions of disease-causing variants discovered in our family are indicated in bold.