PMC9256970_01
Brain MRI findings. (A,B) Bilateral patchy and predominantly frontoparietal white matter hyperintensities with accompanying marked gray matter atrophy are observed on T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging. Cavum septum pellucidum is also evident. (C) Thinning of the corpus callosum is observed on a T1-weighted sequence.
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F1
Brain MRI demonstrated bilateral symmetrical global cortical atrophy (Figure 1).
Genetic findings. (A) A total of 68,272 variants were identified within the targeted exome. Variants of low quality were removed through quality control (GQ <20, RD <10, AF <0.25). Among a panel of 165 genes known to be associated with leukodystrophies and leukoencephalopathies, a total of 484 variants were identified, of which 77 were protein changing or splicing variants. Only 10 of these had an allele frequency <0.10 in gnomAD database, including a novel heterozygous missense variant in the CSF1R gene (B) This change in a highly conserved amino acid in the CSF1R tyrosine domain (p.Gly872Arg), was predicted to be deleterious by multiple in silico tools.
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F2
WES revealed a novel heterozygous missense variant c.2614G>A (p.Gly872Arg) in the CSF1R gene (Figure 2).