Two novel mutations of the NOTCH3 gene in Korean patients with CADASIL.
Mutations in the NOTCH3 gene (NOTCH3) are responsible for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), an adult-onset hereditary angiopathy leading to ischemic episodes, vascular dementia and other neurologic deficits. All mutations of NOTCH3 described so far are strictly stereotyped, leading to the gain or loss of a cysteine residue in a given epidermal growth factor (EGF)-like repeat of NOTCH3. We report two novel mutations of NOTCH3, R587C and C988Y, each resulting in an odd number of cysteine residues in an EGF-like repeat of NOTCH3. We identified these mutations in two unrelated Korean families with CADASIL, who presented with magnetic resonance imaging (MRI) abnormalities typical of CADASIL. These findings confirm that mutations in NOTCH3 are associated with the pathogenesis of CADASIL across different ethnic backgrounds.
Kim
Youngho
Y
Department of Biochemistry, School of Medicine, Wonkwang University, 344-2, Sinyong-Dong, Iksan City, Jeollabuk-Do 570-749, Republic of Korea. youngkim@wonkwang.ac.kr
Kim
Jong Sung
JS
Kim
Guhwan
G
No
Young Joo
YJ
Yoo
Han-Wook
HW
D046589:CADASIL / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007723:Korea; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics*
C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch