PMC6541038_01
(1-1) Neuroimaging findings of the proband. (A,B) Brain T2W-Flair and DWI MRI showed multiple, patchy, symmetrical, and hyperintense lesions in periventricular areas, the corpus callosum, and deep white matter regions of the frontal and parietal lobes. The splenium of the corpus callosum showed a homogeneous hyperintense signal in both Flair and DWI. (C,D) Four months after onset, the MRI abnormal signal became more widespread and confluent. (1-2) Neuropathological findings of the proband. (A,B) The H&E stained section of the brain biopsy showed white matter lesions with myelin and axon damage and neuroaxonal swelling (spheroid formation), accompanied by gliosis prominent in the frontal lobe. (C-G) The activated microglia and phagocytic cells appeared to be segregated. (H) Electron microscopy showed loss of myelin and abnormal axons. Spheroids had thin and discontinuous myelin sheath or no myelin sheath. (I) Large numbers of neurofilaments and organelles were observed in the axoplasm.
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An MRI scan also showed enlarged lateral ventricles (Figures 1-1A-D). Histopathological examination of brain biopsy showed white matter lesions with myelin and axon damage and neuroaxonal swelling (spheroid formation), accompanied by prominent gliosis in the frontal lobe (Figures 1-2A,B). The activated microglia and phagocytic cells appeared to be segregated (Figures 1-2C-G). The axons were swollen and spherical (Figure 1-2H). Large numbers of neurofilaments and organelles were observed in the axoplasm (Figure 1-2I).
Mutation analysis and identification of the c.1858+1G>T mutation of the CSF1R gene. (A) Sequence chromatograms from parts of the CSF1R gene of this case. It displays a splice-site mutation (c.1858+1G>T) in intron 13 of CSF1R. (B) Pedigree of the family studied in this report. The affected individuals are indicated with filled squares and circles. The proband is indicated with an arrow. A plus sign indicates that DNA was examined for the CSF1R sequencing analysis.
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The same mutation was found in his mother (I:2), brother (II:3), the second elder sister (II:6), and his son (III:5), indicating an autosomal dominant pattern of inheritance (Figure 2B).
PMC6541038_02
Mutation analysis and identification of the c.1858+1G>T mutation of the CSF1R gene. (A) Sequence chromatograms from parts of the CSF1R gene of this case. It displays a splice-site mutation (c.1858+1G>T) in intron 13 of CSF1R. (B) Pedigree of the family studied in this report. The affected individuals are indicated with filled squares and circles. The proband is indicated with an arrow. A plus sign indicates that DNA was examined for the CSF1R sequencing analysis.
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The same mutation was found in his mother (I:2), brother (II:3), the second elder sister (II:6), and his son (III:5), indicating an autosomal dominant pattern of inheritance (Figure 2B).
Hyperintense lesions within the white matter were found in the patient's family members carrying the mutation. (A) I:2. (B) II:3. (C) II:6. (D) III:5.
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Hyperintense lesions within the white matter were found in his mother (Figure 3A), elder brother (Figure 3B), and elder sister (Figure 3C), but much less than this patient, indicating that this mutation had different penetrance among family members. The 14-year-old son had normal brain images so far (Figure 3D).