PMC9813394_01
Brain axial images of the first HTRA1-CSVD patient. A DWI image showing an acute infarct in the right basal ganglia (A), and the second acute infarct in the region next to the left lateral ventricle (B), axial T2-weighted (C), and FLAIR axial images (D) showing diffuse WMLs, Fazekas scale score 2, lacunar lesions in bilateral regions next to the lateral ventricle, and an SWI image (E) showing chronic microbleeds in the deep white matter. (F) Validation of a heterozygous G to T mutation at position 1,096 (NM_002775: c.1096G>T) in exon 6 of the HTRA1 gene, resulting in a stop codon at 366 (p.E366X). FLAIR, fluid attenuated inversion recovery; MRI, magnetic resonance imaging; DWI, diffusion-weighted imaging; SWI, susceptibility-weighted imaging.
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F1
Brain MRI showed an acute infarct in the right basal ganglia on DWI images (Figure 1A), diffuse WMLs, Fazekas scale score 2, bilateral lacunar lesions in regions close to the lateral ventricle on T2W/FLAIR, and chronic microbleeds in the deep white matter on SWI images. Brain MRI showed acute infarct in the region next to the left lateral ventricle on DWI (Figure 1B), diffuse WMLs and chronic microbleeds were the same as previously reported. Prompted by the unusual clinical phenotype and neuroimaging findings, a hereditary form of CSVD was suspected (Figures 1C-E). Whole-exome sequencing identified a novel heterozygous HTRA1 nonsense mutation (NM_002775: C.1096G>T; p.E366X) (Figure 1F).
PMC9813394_02
Brain axial images of the second patient. A DWI image showing an acute infarct in the left corona radiata (A), axial T2-weighted (B) and FLAIR axial images (C, D) showing diffuse WMLs and brain atrophy, Fazekas scale score 3, and an SWI image showing chronic microbleeds in lobar regions and the deep white matter (E). (F) Validation of a heterozygous G to T mutation at position 151 (NM_002775: c.151G>T) in exon 1 of the HTRA1 gene, resulting in a stop codon at 51 (p.E51X).
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F2
WMLs and brain atrophy (Figures 2A-E), whole-exome sequencing was performed. Whole-exome sequencing identified a novel heterozygous nonsense mutation (NM_002775: c.151G>T; p.E51X) (Figure 2F).