Abstract
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary cerebral small vessel disease caused by mutations in NOTCH3, is characterized by recurrent stroke without vascular risk factors, mood disturbances, and dementia. MRI imaging shows cerebral white matter (WM) hyperintensity, particularly in the external capsule and temporal pole. Missense mutations related to a cysteine residue in the 34 EGFr on the NOTCH3 extracellular domain (N3ECD) are a typical mutation of CADASIL. On the other hand, atypical mutations including cysteine sparing mutation, null mutation, homozygous mutation, and other associate genes are also reported. From the viewpoint of gain of function apart from Notch signaling or loss of function of Notch signaling, we review the research article about CADASIL and summarized the pathogenesis of small vessel, stroke, and dementia in this disease.
Highlights
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the most common hereditary cerebral small vessel diseases caused by mutations in NOTCH3
This review article is summarized in terms of whether CADASIL is caused by the gain of NOTCH3 function or by loss of NOTCH signaling function
Fouillade et al (2008) reported a 53-year-old woman with 35-years-onset stroke and MRI finding of white matter (WM) hyperintensity. They identified NOTCH3 c.4544T>C resulting in p.L1515P mutation which localizes in the C-terminal end of NOTCH3 extracellular domain (N3ECD)
Summary
Toshiki Mizuno*, Ikuko Mizuta , Akiko Watanabe-Hosomi , Mao Mukai and Takashi Koizumi. Edited by: Satoshi Saito, National Cerebral and Cardiovascular Center (Japan), Japan. Reviewed by: Yumi Yamamoto, National Cerebral and Cardiovascular Center (Japan), Japan Sabina-Capellari, University of Bologna, Italy. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary cerebral small vessel disease caused by mutations in NOTCH3, is characterized by recurrent stroke without vascular risk factors, mood disturbances, and dementia. Missense mutations related to a cysteine residue in the 34 EGFr on the NOTCH3 extracellular domain (N3ECD) are a typical mutation of CADASIL. Atypical mutations including cysteine sparing mutation, null mutation, homozygous mutation, and other associate genes are reported. From the viewpoint of gain of function apart from Notch signaling or loss of function of Notch signaling, we review the research article about CADASIL and summarized the pathogenesis of small vessel, stroke, and dementia in this disease
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