PMC5030299_01
Pedigree of the studied Chinese family. The proband is indicated by the arrow. Squares represent males; circles represent females. Black-filled symbols indicate a member showing multiple cerebral cavernous malformations upon SWI-MRI of the brain. A diagonal line through the symbol represents a deceased person.
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F1
T2-weighted gradient echo (GRE) sequences (Figures 2B,C). The diameters of the lesions ranged from 0.5 mm to 3 cm, averaging 0.9 cm. The patient's elder brother (Figure 1 II-2, aged 63 years) and younger sister (Figure 1 II-3, aged 53 years) were asymptomatic.
CCM lesions diagnosed through CT, GE-and SWI-MRI. (A) CT of the 57-year-old proband, II-1. A plain CT scan (brain window images) showed multiple calcification spots scattered on the tegmentum of the pons, temporal lobes and periventricular area. (B) Axial T1-weighted gradient-echo (GE) MR imaging of the proband, II-1. Axial T1-weighted GE images demonstrated hyper-intensity of hemorrhage lesions. (C) Axial T2-weighted gradient-echo (GE) MR imaging of the proband, II-1. T2-weighted GE images showed a "popcorn" appearance surrounded by a dark rim of hemosiderin. (D) SWI-MR imaging of the proband, II-1. SWI revealed thickly dotted CCMs distributed throughout the cerebral cortex in the brain of the proband. There are dozens of lesions on the cerebrum, cerebellum, thalamus, and brain stem. The diameter of the lesions ranges from a few millimeters to several centimeters. (E) SWI-MR imaging of the proband's elder brother, II-2. II-2 showed a similar phenomenon, with multiple CCM lesions observed upon SWI-MRI of the brain. (F) SWI-MR imaging of the proband's younger sister, II-3. II-3 did not show any CCM lesions upon SWI-MRI of the brain.
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Non-contrast computed tomography revealed multiple high-intensity patchy calcifications or bleeding distributed around the cortical and subcortical regions of the cerebral hemispheres, cerebellum and brain stem (Figure 2A). Surprisingly, many additional thick CCMs distributed throughout the brain (including the cerebrum, cerebellum, thalamus, and brain stem) were detected in susceptibility-weighted images (SWIs, Figure 2D). T2-weighted gradient echo (GRE) sequences (Figures 2B,C). The diameters of the lesions ranged from 0.5 mm to 3 cm, averaging 0.9 cm. The patient's elder brother (Figure 1 II-2, aged 63 years) and younger sister (Figure 1 II-3, aged 53 years) were asymptomatic. Although the proband's elder brother (II-2) did not presented much more and severer CCM lesions on the cerebellum, cerebrum, thalamus, and brain stem than the proband, he also showed a similar phenomenon, with multiple CCM lesions in sections of the sellar region and parietal lobe upon sagittal and coronal SWI imaging of the brain (Figure 2E). The proband's sister (II-3) did not show any CCMs in the SWI scan of the brain (Figure 2F).
Distribution and function of mutations in the CCM2 gene. (A) Schematic representation of four CCM2 gene mutations identified in the domains of CCM2-coding protein in the studied Chinese family with FCCM. (B) A novel frameshift mutation in exon 2 of the CCM2 gene. This deletion (c.95 delC), located in exon 2, was heterozygous in both siblings with CCMs. It resulted in a stop codon in the 36th original codon and produced a 35-amino acid, truncated form of CCM2, without the PTB domain and all of the C-terminal domains.
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T2-weighted gradient echo (GRE) sequences (Figures 2B,C). The diameters of the lesions ranged from 0.5 mm to 3 cm, averaging 0.9 cm. The patient's elder brother (Figure 1 II-2, aged 63 years) and younger sister (Figure 1 II-3, aged 53 years) were asymptomatic.