Kim Youngho, Kim Jong Sung, Kim Guhwan, No Young Joo, Yoo Han-Wook
Department of Biochemistry, School of Medicine, Wonkwang University, 344-2, Sinyong-Dong, Iksan City, Jeollabuk-Do 570-749, Republic of Korea.
Mutat Res. 2006 Jan 29;593(1-2):116-20. doi: 10.1016/j.mrfmmm.2005.06.031. Epub 2005 Oct 26.
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.
NOTCH3基因（NOTCH3）突变是导致伴有皮质下梗死和白质脑病的大脑常染色体显性动脉病（CADASIL）的原因，CADASIL是一种成年起病的遗传性血管病，可导致缺血性发作、血管性痴呆和其他神经功能缺损。迄今为止描述的NOTCH3所有突变都具有严格的模式化特征，导致NOTCH3特定表皮生长因子（EGF）样重复序列中半胱氨酸残基的增减。我们报告了NOTCH3的两个新突变，R587C和C988Y，每个突变都导致NOTCH3的一个EGF样重复序列中半胱氨酸残基数量为奇数。我们在两个不相关的患有CADASIL的韩裔家族中发现了这些突变，他们的磁共振成像（MRI）表现出CADASIL典型的异常。这些发现证实，NOTCH3突变在不同种族背景中均与CADASIL的发病机制相关。
