NOTCH3 and infantile myofibromatosis: Notably, a NOTCH3L1515P mutation produces a NOTCH3 receptor with enhanced signaling and secretion of the ECD and has been linked to cerebral SVD.31 Similarly, a NOTCH3L1519P mutation, which is found in a family with infantile myofibromatosis,32 generates a ligand-independent hyperactive form of NOTCH3.33,38 At this stage, however, we cannot formally exclude any of the hypotheses, and how the mutation may directly affect S2 processing remains to be tested.