A: Coronal MR imaging of a patient with the C455R mutation in NOTCH3 shows characteristic white matter lesions (arrowheads). Image courtesy of Dr. Francisco Lopera (University of Antioquia, Colombia). B: Electron micrographs of subcortical white matter of postmortem brains from an individual carrying the C455R mutation shows abundant electron-dense granular osmiophilic (GOM) deposits (arrows). Scale bars: (A) 1.4 cm; (B) 2 μm.
C: Structure of the Notch 3 receptor. A schematic of the receptor indicating key structural features. The 34 Epidermal Growth Factor-like (EGF-like) repeats and the 3 Lin12-Notch repeats (LNR) are indicated in the extracellular domain. The transmembrane (TM), and the intracellular RAM, ankyrin repeat region (ANK), TAD, and PEST domains are also shown (top). Distribution of known CADASIL mutations along the EGF-like repeats (bottom). The relative size of circles below the schematic indicates the number of mutations reported for each cluster of EGF repeats.