MAF in database and prediction of functional change of identified RNF213 variants.

<p>MAF in database and prediction of functional change of identified RNF213 variants.</p

Migration assay using HUVECs transfected with <i>RNF213</i> D4013N, R4019C and V4146A.

<p>Representative images are shown in upper panel. The re-endothelialized areas were quantified by imaging analysis (lower panel). “Vector” represents backbone vector, not including <i>RNF213</i>. Data with bars represent mean ± SD (<i>n</i> = 3 or 4). *<i>P</i> < 0.05 compared with vector, #<i>P</i> < 0.05 compared with WT according to Student’s <i>t</i>-test.</p

Imaging data of II-2 in Family 1.

<p>(A) MRA image. TOF-3D MRA verifies typical steno-occlusive changes of the circle of Willis. Distal T segments of both internal carotid arteries are occluded and basal moyamoya vessels are clearly seen (anteroposterior view, left panel). Typical “puff-of-smoke” look of moyamoya vessels. Internal carotid arteries are relatively hypoplastic compared with the vertebrobasilar system (lateral view, right panel). (B) Digital subtraction angiography. Catheterization angiography of left vertebral artery (left panel), left carotid artery (middle panel), and right carotid artery (right panel). (C) Transcranial color-coded sonography. Severely dampened flow in the M1 segment of the left middle cerebral artery.</p

Homology of identified RNF213 variants.

<p>Homology of identified RNF213 variants.</p

Identification of <i>RNF213</i> rare variants in three families.

<p>(A) Pedigree chart and genotypes of <i>RNF213</i> rare variants and microsatellite markers of the three families. Filled and unfilled symbols indicate affected and unaffected individuals, respectively. Squares and circles represent males and females, respectively. Arrows indicate index case. (B) Sequence chromatography of the identified <i>RNF213</i> rare variants. (C) Haplotype for p.R4019C and p.E4042K determined by cloning in II-1 in Family 2.</p

Schematic diagram of <i>RNF213</i> rare variants identified in MMD patients.

<p>Variants in Asian and white patients are shown above and below the protein, respectively. The five variants identified in MMD patients from this study are shown in bold characters. AA, amino acid; AAA+, ATPase associated with diverse cellular activities domain; RING, RING-finger domain. This figure was modified from the original version described in Reference 6.</p

Tube formation assay of HUVECs transfected with <i>RNF213</i> D4013N and V4146A.

<p>Representative images are shown in upper panel. The tube areas, total tube length, and number of tube branches were quantified by imaging analysis (lower panel). “Vector” represents backbone vector, not including <i>RNF213</i>. Data with bars represent mean ± SD (<i>n</i> = 3). *<i>P</i> < 0.05 compared with vector, #<i>P</i> < 0.05 compared with WT, †<i>P</i> < 0.05 compared with D4013N according to Student’s <i>t</i>-test.</p