Editing CADASIL (section)

==Pathophysiology==
The underlying pathology of CADASIL is progressive hypertrophy of the [[smooth muscle tissue|smooth muscle cells]] in [[blood vessel]]s. [[Dominance (genetics)|Autosomal dominant]] mutations in the ''[[NOTCH3]]'' gene (on the long arm of chromosome 19) cause an abnormal accumulation of Notch 3 protein at the [[cytoplasmic]] membrane of vascular smooth muscle cells both in [[cerebrum|cerebral]] and extracerebral vessels,<ref>{{cite journal|vauthors=Joutel A, Andreux F, Gaulis S |title=The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients |journal=J. Clin. Invest. |volume=105 |issue=5 |pages=597–605 |date=March 2000 |pmid=10712431 |pmc=289174 |doi=10.1172/JCI8047 |display-authors=etal}}</ref> seen as granular [[osmiophilic]] deposits on [[electron microscopy]].<ref>{{cite journal |vauthors=Ruchoux MM, Guerouaou D, Vandenhaute B, Pruvo JP, Vermersch P, Leys D |title=Systemic vascular smooth muscle cell impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy |journal=Acta Neuropathol. |volume=89 |issue=6 |pages=500–12 |year=1995 |pmid=7676806|doi=10.1007/BF00571504|s2cid=24884723 }}</ref> [[Leukoencephalopathy]] follows. Depending on the nature and position of each mutation, a consensus significant loss of [[beta sheet]] structure of the Notch3 protein has been predicted using [[in silico]] analysis.<ref>{{cite journal|vauthors=Vlachakis D, Champeris Tsaniras S, Ioannidou K, Papageorgiou L, Baumann M, Kossida S |title=A series of Notch3 mutations in CADASIL; insights from 3D molecular modelling and evolutionary analyses |journal=Journal of Molecular Biochemistry |volume=3 |issue=3 |pages=97–105 |date=October 2014}}</ref>