PMC3972264_01
Manifestation of vaccine strain varicella zoster virus-induced central nervous system vasculopathy. Axial diffusion weighted magnetic resonance image obtained after onset of neurological symptoms demonstrated scattered sites of acute ischemia involving the parasagittal cortices bilaterally and the left perirolandic cortex (panel A). Three-dimensional time of flight magnetic resonance angiographic image of the circle of Willis revealed multifocal stenotic anterior cerebral (short arrow), anterior communicating (dashed arrow), and middle cerebral (long arrows) arteries (panel B). Post-contrast T1W black blood arterial wall image illustrated avid enhancement and thickening of the distal supraclinoid internal carotid arterial walls bilaterally (panel C, arrows).
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F1
Repeat MRI with axial diffusion-weighted images revealed multiple areas of acute infarction in areas supplied by both anterior cerebral arteries, a branch of the anterior cerebral artery, the right posterior cerebral artery, and the left middle cerebral artery (Figure 1A). Subsequent 3-dimensional time of flight magnetic resonance angiographic imaging of the circle of Willis revealed vascular narrowing and post-stenotic dilatation (Figure 1B). Post-contrast T1W black blood arterial wall imaging illustrated avid enhancement and thickening of the distal supraclinoid internal carotid arterial walls bilaterally (Figure 1C).
DOCK8 molecular analyses. A single base pair mutation at exon 12, resulting in a frame shift and premature stop codon: c.1266delC   p.Y423TfsX18, based upon reference sequence NM_00193536.1, isoform 3, was identified by DOCK8 gene sequencing, in addition to a large deletion on the opposite allele by clinical comparative genetic hybridization (panel A). T cells from the patient failed to express DOCK8 protein (panel B). Cell lysates were prepared from the patient (lane 2), parents (lanes 3, 4) and a healthy control (lane 1). Lanes were each loaded with 30 mug of protein. Immunoblotting for DOCK8 or actin proteins was performed as described.
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F2
PCR analysis of genomic DNA and DOCK8 gene sequencing identified a single base pair mutation on the opposite allele at exon 12, resulting in a frame shift and premature stop codon: c.1266delC, p.Y423TfsX18, based upon reference sequence NM_00193536.1, isoform 3 (Figure 2A). Western Blot analysis confirmed lack of DOCK8 protein expression (Figure 2B).