Figure 1.

Characterization of damaging de novo mutations in patients with hypoplastic left heart syndrome. A, Waterfall plot of de novo multihit genes (red) or gene family (bold) identified in the hypoplastic left heart syndrome (HLHS) cohort. “Multihit” refers to the occurrence/presence of variants in the same gene or family of genes among different individuals. Additional de novo genes in each subject are in plain black. B, Cell type–specific expression of HLHS damaging de novo mutation (D-DNM) genes based on single-cell RNA sequencing from normal fetal hearts between 4.5 and 25 weeks (W) of gestation. Data from Ciu et al.²⁹ and Sahara et al.²⁸ were used to generate the upper and lower heatmap, respectively. C and D, Bar chart of Gene Ontology (GO) enrichment analysis (C) and protein–protein network analysis (D) of D-DNM genes. In D, each Netbox module is coded by a different color, with mutated genes illustrated as circles and linker genes as diamonds. CM indicates cardiomyocytes; CP, cardiac progenitor; ECM, extracellular matrix; EndC, endothelial cells; EpiC, epicardial cells; ER, endoplasmic reticulum; FB, fibroblasts; HGNC, HUGO Gene Nomenclature Committee; IM, intermediates; OFT, outflow tract; ValvC, valvular cells; and Vent, ventricular.