SLC4A11 and the Pathophysiology of Congenital Hereditary Endothelial Dystrophy

Figure 1

Cartoon of SLC4A11 protein topology showing the location of CHED-linked missense mutations. Approximately half of the individuals identified with CHED-linked mutations in SLC4A11 carry homozygous nonsense, frameshift, deletion, or splice-site mutations (not shown) that are predicted to result in the loss of active SLC4A11 protein. The other half carry homozygous missense mutations (colored circles) that are predicted to alter the protein sequence of SLC4A11 protein, noting the site of residues that are presumably important for the correct folding and activity of SLC4A11. Six individuals with CHED carry compound heterozygous (CH) mutations in SLC4A11: the location of missense mutations that have only been described in these individuals, and not in homozygous form, is marked with colored diamonds. The color of the circles and diamonds denotes the number of cases in which the mutation has been observed. Moving from amino- to carboxyterminus, the single cases (yellow) are R125H, E143K, S232N (CH with R329X), R233C, T262I, T271M, G394R, E399K, T401K (CH with L473R), L473R (CH with T401K), R488K, C611R, G709E, H724D, T754M, R804M, M856V (CH with S213P), and L873P. Sites mutated in two instances (orange) are R209W, S213L (plus CH S213P/M856V), A269V, C386R, G417R, G4181D, S489L, T584K (plus CH T548K/R112X), T833M, and L843P (both instances in CH form with frameshift mutations). Sites mutated in three instances (red) are A160T, G464D, P773L (including CH P773L/R112X), and V824M. Note that homozygous inheritance of A160T has also been observed in one unaffected individual and thus may not be the exclusive cause of CHED in these individuals [4]. Sites mutated in seven or more instances (black) are R755Q/R (including five instances of R755Q, one CH case of R755Q/R875X, and four instances of R755W) and R869C (seven instances). References: [4–16].