(A) Images from a 36-month-old control and (B) 3 different time points of patient with miR-145-5p mutation. MRA images are anterior-posterior [AP] and lateral MIP. Note increased angulation of the forceps of the corpus callosum (red arrows) and significant bilateral periventricular and right watershed white matter injury (yellow arrows) at age 33 months, which progressed to bilateral white matter (yellow arrows) and right frontal ischemic infarctions (green arrows) by 8 years of age. Additional arterial ischemic infarctions occurred through 17 years of age. Vascular anatomy showed straightening and decreased caliber of the terminal internal carotid artery (ICA) and basal cerebral arteries with progression of the relative stenosis of the terminal ICA (red bar) when compared with its petrous segment. (C) Variant in the MIR145 gene shown as primary structure in multiple species comparison and in secondary structure. (D and E) Vascular SMCs transduced with indicated miRs, analyzed by Western blotting and immunofluorescence, demonstrate that the mutant version of miR-145-5p fails to mediate contractile protein expression or induce stress fiber formation similar to WT miR-145-5p. *Sequence conservation across species.