Fig. 2

Pathogenic variants identified in cohort of Southeast Asian CI patients. Schematic representation of mutated gene domains with annotated missense, nonsense, splicing, and frameshift mutations identified in affected individuals with ABCA12, TGM1, KRT1, FLG, ERCC2, VSP33B, and ALDH3A2 mutations. “Coupling mutations” refers to variants identified together in the same patient. Variants highlighted with yellow experienced sepsis: we note that most of sepsis cases happened with double mutation, while 70% of the ABCA12 variants associated with sepsis in our cohort were adjacent to the ABC1 or ABC2 domains; KRT1 G488V variant associated with sepsis occurred at the C-terminus in the highly conserved TYR*LLEGE motif known to be critical for intermolecular and higher order filament interactions (see Additional file 3: Fig. S2); IV patients who experienced sepsis had either frameshift or nonsense mutations in the N-terminal half of FLG whereas those having mutations more C-terminal did not experience sepsis