PMC9932685_01
Cranial magnetic resonance imaging of this patient: (A-C) cross-sectional sequences of T2-weighted image (T2WI) (A,B) and sagittal image of T1-weighted image (T1WI) (C) (17 December 2019) showed the encephalomalacia in the right basal ganglia, frontal lobe and cerebral atrophy. (D-F) Cross-sectional sequences and sagittal images of T2WI (31 August 2021) showed that encephalomalacia foci had expanded to bilateral frontal lobe, right insula, and right temporo-occipital junction; brain atrophy is more worse than before. (G) Diffusion-weighted imaging (DWI) sequence showed punctate hyperintensity singals on the right cerebellum (22 September 2021). (H,I) DWI sequences showed abnormally high signal intensity on left parietal-occipital junction, and the left cerebellum (10 October 2021).
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F1
October 2021) showed abnormally high signal intensity in the DWI sequence of the left parietal-occipital junction, and left cerebellar hemisphere, suggesting a new acute cerebral infarction (Figures 1H, I).
PMC9932685_02
Cranial magnetic resonance imaging of this patient: (A-C) cross-sectional sequences of T2-weighted image (T2WI) (A,B) and sagittal image of T1-weighted image (T1WI) (C) (17 December 2019) showed the encephalomalacia in the right basal ganglia, frontal lobe and cerebral atrophy. (D-F) Cross-sectional sequences and sagittal images of T2WI (31 August 2021) showed that encephalomalacia foci had expanded to bilateral frontal lobe, right insula, and right temporo-occipital junction; brain atrophy is more worse than before. (G) Diffusion-weighted imaging (DWI) sequence showed punctate hyperintensity singals on the right cerebellum (22 September 2021). (H,I) DWI sequences showed abnormally high signal intensity on left parietal-occipital junction, and the left cerebellum (10 October 2021).
fgene-14-1072978-g001.jpg
PMC9932685_02_fgene-14-1072978-g001.jpg
F1
October 2021) showed abnormally high signal intensity in the DWI sequence of the left parietal-occipital junction, and left cerebellar hemisphere, suggesting a new acute cerebral infarction (Figures 1H, I).
Multimodality molecular imaging of the patient: (A) Multimodal molecular imaging of 18-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET-CT) results suggested hypometabolism in dorsolateral frontal cortex, dorsolateral parietal cortex, bilateral precuneus, lateral of right temporal lobe and right occipital lobe, and right caudate nucleus. (B) 11-carbon-Pittsburgh positron emission tomography (11C-PIB PET-CT) showed no amyloid plaque deposition in the brain. (C) 18-fluoro-S16-positron emission tomography (18F-Flortaucipir-tau PET-CT) showed tau deposition in bilateral thalamus, caudate nucleus, midbrain, pons, and bilateral medial temporal lobe.
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F2
Multimodal molecular imaging of 18-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET-CT) results suggested hypometabolism in dorsolateral frontal cortex, dorsolateral parietal cortex, bilateral precuneus, lateral of right temporal lobe and right occipital lobe, and right caudate nucleus (Figure 2A). 11-carbon-Pittsburgh positron emission tomography (11C-PIB PET-CT) showed no amyloid plaque deposition in the brain (Figure 2B). 18-fluoro-S16-positron emission tomography (18F-Flortaucipir-tau PET-CT) showed Tau deposition in bilateral thalamus, caudate nucleus, midbrain, pons, and bilateral medial temporal lobe (Figure 2C).
Whole exome sequencing results and family pedigree. (A,B) Both of the patient and his mother carried a heterozygous mutation in WFS1 c.1756G>A p.A586T. (C) Genealogical tree of the patient. [Square, man; circle, woman; black-filled symbol, affected individual (with cognitive impairment); empty symbol, unaffected individual; P (arrow), proband; diagonal black line, deceased; +, individual with WFS1 gene mutation; consanguineous marriage was not observed in this family].
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F3
The whole exome gene sequencing results of the patient and her mother showed that both of them carried a heterozygous missense mutation in WFS1 c.1756G>A (p.A586T) (Figures 3A, B). Therefore, we performed a detailed detailed family history questioning and screening, the patient's mother had clinical manifestations of cognitive decline and emotional anxiety, which were confirmed by the objective neuropsychological scales (the MMSE score is 25, MoCA score is 23 and NPI score is 2). His father and other blood relatives are currently in good health with no complaints of memory loss or clinical manifestations (Figure 3C).