Figure 3. Locations of GFAP mutations in Alexander disease in relation to the protein structure. The four open rectangular boxes represent the helical coiled-coil rod domains of GFAP; these structural motifs are highly conserved among most intermediate filament proteins. The solid lines joining these segments are nonhelical linker regions, and the solid lines at either end are the nonconserved, random coil, N-terminal and C-terminal regions. The gray box just before segment 1A is a nonconserved prehelical sequence important for initiation of rod formation at the start of 1A; the gray box at the end of 2B represents a highly conserved sequence that includes the end of the coiled coil 2B segment. The wild-type amino acid is indicated next to the structure, and amino acid replacements within symbols on either side. Early-onset cases (first symptom before the age of 2 years) are on the left, shown as blue circles, and late-onset cases (first symptom after the age of 2 years) are on the right, shown as red circles. Each symbol represents a single patient, except that familial cases, including identical twins, are represented by a single symbol coded for the onset type of the proband. Adapted with permission from Brenner et al. (2009), their Figure 24.4.