case_images: PMC11192518_01
case_images: a Roman numerals (I, II, III, IV) indicate the generations, and the numbers (1-9) indicate the individuals in each generation. The proband is indicated by the arrow; black-filled symbols represent subjects affected by II.2 by FTD; age at onset: 40 y, age at death: 48 y); II.3: dementing illness similar to the proband, age at onset: 40; age at death: 46 years. Diagonal lines indicate the deceased and asterisk in whom the variant has been demonstrated. The proband is II.2 (filled, arrow, and asterisk), a 45-year-old female, carrying the (c.40 + 1G>A) splice donor variant TREM2. b Chromatogram of the proband highlighted at intron 1 of TREM2 (between exons 1 and 2 of 5) (transcript ID: NM_018965.4). The proband has been identified with homozygous targeted mutation in intron 1 of TREM2 gene (highlighted in blue). c-e T1-weighted multiplanar imaging shows frontoparietal predominant atrophy and ventricular horn prominence. f Axial FLAIR image showing frontoparietal periventricular and deep white matter hyperintense signal changes and volume loss. g SWI demonstrates blooming in the bilateral lentiform nucleus.
case_images: dee-2024-0014-0001-538145_F02.jpg
case_images: PMC11192518_01_dee-2024-0014-0001-538145_F02.jpg
case_images: F2
case_images: There was a history of similar behavioural disturbances in the elder sister who had a premature death as shown in Figure 2. T2/FLAIR hypointensity was observed in the bilateral putamen, globus pallidus, and subcortical FLAIR intensities in the frontal lobe along with a striking thinning of the corpus callosum as shown in Figure 2. This variant was validated on Sanger sequencing as shown in Figure 2.
case_images: PMC11192518_02
case_images: a Family tree: Roman numerals (I, II, III, IV) indicate the generations, and the numbers (1-17) indicate individuals in each generation. The proband is indicated by the arrow; black-filled symbols represent subjects affected by III.7: psychiatric illness; age at onset: 43 y; diagonal lines indicate the deceased and asterisk in whom the variant has been demonstrated. The proband is III.3 (filled, arrow, and asterisk), a 43-year-old female carrying the (p.Gln28Ter*) stop gained variant TYROBP. b Chromatogram showing homozygous stop gained variant in exon 2 of 5 in TYROBP mutation NM_00332.4(TYROBP): C.82C>T(p.Q28*); transcript ID: NM_00332.4. c First image from left is T1-weighted axial images showing frontoparietal atrophy with hypointense periventricular white matter changes. d Second image is T2-weighted axial image showing periventricular white matter hyperintensity. e SWI axial view image showing lenticular nucleus blooming. f NCCT shows ill-defined calcification in bilateral lentiform nuclei. g, h AP and lateral X-ray of the bilateral hands and wrists show multiple variable size ill-defined trabecular lucencies, a few of which have a cystic morphology in a periarticular and metaphyseal distribution. i, j AP and lateral X-ray of the bilateral legs and ankle show multiple variable size ill-defined trabecular lucencies, a few of which have a cystic morphology in a periarticular and metaphyseal distribution.
case_images: dee-2024-0014-0001-538145_F03.jpg
case_images: PMC11192518_02_dee-2024-0014-0001-538145_F03.jpg
case_images: F3
case_images: Family history of psychiatric illness with onset at 43 years was present in her first cousin as shown in Figure 3. X-rays of hands, wrists, legs, and ankles showed multiple variable size ill-defined trabecular lucencies, with a few demonstrating cystic morphology in a periarticular and metaphyseal distribution as shown in Figure 3. This variant has been Sanger validated as shown in Figure 3.
case_images: PMC11192518_03
case_images: a Chromatogram of the proband highlighted at intron 14 of CSF1R (between exons 14 and 15 of 22) (transcript ID: NM_05211.4). The proband has been identified with heterozygous targeted mutation in intron 14 of CSF1R gene (highlighted in blue). b T1-weighted multiplanar imaging shows frontoparietal predominant atrophy and ventricular horn prominence. c Axial FLAIR images reveal frontoparietal periventricular and deep white matter hyperintense signal changes and volume loss. d DWI has evidence of multifocal scattered areas of diffusion restriction in the bilateral frontal and parietal deep white matter. e NCCT scan brain shows periventricular hypodensity.
case_images: dee-2024-0014-0001-538145_F04.jpg
case_images: PMC11192518_03_dee-2024-0014-0001-538145_F04.jpg
case_images: F4
case_images: Imaging revealed T1, T2, FLAIR, and DWI hyperintense signal changes in the white matter periventricular region, centrum semiovale, corona radiata, and corpus callosal atrophy with diffusion restriction in the splenium along with diffuse atrophy as shown in Figure 4. Sanger validation confirmed the genetic variation as shown in Figure 4.
case_images: PMC11192518_04
case_images: a Sagittal T2-weighted image reveals moderate cerebral atrophy. b-d Axial T2-weighted images show moderate frontal and parietal atrophy with mild temporal atrophy and relative occipital sparing. e, f Axial FLAIR images reveal frontoparietal periventricular and deep white matter hyperintense signal changes. g SWI demonstrates no blooming. h, i DWI has no evidence of diffusion restriction. j T1-weighted multiplanar imaging shows parietal predominant atrophy. k, l PET imaging shows hypometabolism in the bilateral temporoparietal and lateral occipital regions. m Sanger sequencing electropherogram showing heterozygous variant at c.2768A>G position in CSF1R mutation of the proband's sample.
case_images: dee-2024-0014-0001-538145_F05.jpg
case_images: PMC11192518_04_dee-2024-0014-0001-538145_F05.jpg
case_images: F5
case_images: MR showed hypometabolism in the temporoparietal and posterior cingulate region as shown in Figure 5. MR images also showed bifrontal asymmetric T2-weighted/FLAIR hyperintensities in the subcortical deep and periventricular white matter with corresponding T1 hypointensities. SUB13901225. Sanger sequencing electropherogram revealed heterozygous variant at c.2768A>G position in the proband's sample as depicted in Figure 5.
case_images: PMC11192518_05
case_images: a-c Axial T2-weighted images show gliosis at bilateral temporal poles, basifrontal regions, left superior frontal and right superior parietal lobule region with frontal depressed fracture on the left side. d Haemorrhagic residue is seen in these locations on SWI. e, f Gliosis is demonstrated on FLAIR images in these locations. g No diffusion abnormality is seen. h T1-weighted image shows mild diffuse cerebral atrophy. i-l PET images show hypometabolism in the gliotic foci. m Sanger sequencing electropherogram confirmed heterozygous variant at c.658G>A (p. Ala220Thr) in CSF1R mutation of the proband's sample (Fig. 6).
case_images: dee-2024-0014-0001-538145_F06.jpg
case_images: PMC11192518_05_dee-2024-0014-0001-538145_F06.jpg
case_images: F6
case_images: Serial neuroimaging revealed progressive white matter hyperintensities in bilateral frontoparietal region as shown in Figure 6. Ala220Thr) in the proband's sample (Fig. 6).