PMC6851058_01
Axial and coronal FLAIR MRI show signal hyperintensity prevalent in the cerebral posterior periventricular regions (arrows in A,B) and in the hilum of the dentate nuclei (arrow in C). Midbrain and pons show peripheral rim of hyperintensity (arrow in D). Axial T2-weighted sections show increased signal intensity in the hilum of the dentate nuclei (arrow in E). A sagittal T2-weighted image shows atrophy and signal change in the medulla and spinal cord, "tadpole sign" (arrow in F).
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F1
Periventricular hyperintensity was observed on fluid attenuation inversion recovery (FLAIR) MRI (Figure 1). Paradoxical respiration is shown in Supplementary Figure 1.
(A) The GFAP exon 1 sequence, obtained from a control (top) and our patient (bottom). The bottom picture shows heterozygosity for the missense c.219G>C nucleotide change, corresponding to the p.M73I mutation. (B) Representative images showing HeLa cells transiently transfected with plasmids encoding human wild-type GFAP or mutant GFAP M73I and R239C and labeled with GFAP antibody. The image shows wild-type GFAP assembled in filament networks, whereas mutant M73I and R239C formed dot-like aggregates. On the right, a detail is given of the Sanger sequences of the plasmids encoding wild-type GFAP and GFAP M73I; codon 73 was mutated from ATG (Met) to ATC (Ile).
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F2
Genetic analysis of the GFAP gene detected a heterozygous mutation in exon 1 (c.219G>C), resulting in an amino acid exchange at codon 73 from methionine to isoleucine (p.M73I) (Figure 2A). The proportion of cells transfected with M73I-GFAP and R239C-GFAP showing GFAP aggregates was 100% (n = 170 HeLa cells transfected with wild-type-GFAP, n = 148 cells transfected with M73I-GFAP, n = 172 cells transfected with R239C-GFAP, Chi-square 490.0, df 2, p < 0.0001, Figure 2B).