case_images: PMC10296183_01
case_images: (A) Axial views of the fluorodeoxyglucose (FDG)-positron emission tomography (PET) acquired at month 18 from symptom onset. Images show hypometabolism in the left fronto-insular, fronto-temporal and temporo-lateral regions, and in the basal-ganglia with a left predominance. (B) Coronal and axial views of the 3DT1-weighted MR images acquired at month 24 from symptom onset. Images show left sylvian-perisylvian, fronto-opercular, parietal and striatal atrophy. (C) Axial view of the FLAIR image acquired at month 24 from symptom onset. The image shows prevalent left frontal periventricular white matter hyperintensities. (D) Axial view of the FLAIR image acquired at month 31 from symptom onset. The image shows a progressive ventricular enlargement mainly at the left side and increased burden of left frontal white matter hyperintensities. Images are displayed according to standard radiological convention. R, right.
case_images: fnins-17-1204504-g001.jpg
case_images: PMC10296183_01_fnins-17-1204504-g001.jpg
case_images: fig1
case_images: FDG-PET showed hypometabolism in the left fronto-insular, fronto-temporal, and temporo-lateral regions, and in the basal-ganglia with a left predominance (Figure 1A). Brain 3 T MRI reported left sylvian-perisylvian, fronto-opercular, parietal, and striatal atrophy and prevalent left frontal periventricular white matter hyperintensities (WMHs; Figures 1B,C). Compared to the first one, the second 3 T MRI examination revealed a progressive ventricular enlargement mainly at the left side with more atrophy of the left frontal-opercular and temporo-mesial regions, and increased burden of left frontal WMHs (Figure 1D).
case_images: Schematic representation of impaired language (A), extra-language domains (B), and conducted writing (C) of the patient at month 24 and 31 from symptom onset. Green color indicates normal abilities, red color indicates impaired abilities.
case_images: fnins-17-1204504-g002.jpg
case_images: PMC10296183_01_fnins-17-1204504-g002.jpg
case_images: fig2
case_images: At this time, the patient also showed mild non-linguistic deficits, such as orofacial apraxia, and difficulties in the attribution of others' intentions and emotions (Table 1; Figure 2A). Language deficits worsened, also including disturbances in single-word comprehension, object knowledge, and sentence repetition (see Figure 2C which reports the rapid progression of language impairment for the conducted writing). Figure 2B), with a severe involvement of attention and executive functions. Furthermore, the partner of the patient referred moderate levels of apathy, aspontaneity, hyperorality, and preference for sweet foods.
case_images: Sequencing chromatogram of GRN from the proband showing the heterozygous variant c.1018delC. The red arrow shows the C deletion in 1018 position in exon 10 introducing premature stop codon p.H340TfsX21 (Homo sapiens, Reference sequence ENSG00000030582.18, LRG_661). WT, wild type.
case_images: fnins-17-1204504-g003.jpg
case_images: PMC10296183_01_fnins-17-1204504-g003.jpg
case_images: fig3
case_images: The genotyping revealed a new heterozygous GRN c.1018delC mutation (p.H340TfsX21), which determined the shift of amino acid 340 and, consequently, the introduction of a premature stop codon after 21 amino acids in the encoded protein of the GRN gene (Figure 3).