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Two novel mutations of the NOTCH3 gene in Korean patients with CADASIL

Youngho Kim1, Jong Sung Kim, Guhwan Kim

  • 1Department of Biochemistry, School of Medicine, Wonkwang University, 344-2, Sinyong-Dong, Iksan City, Jeollabuk-Do 570-749, Republic of Korea. youngkim@wonkwang.ac.kr

Mutation Research
|November 1, 2005
PubMed

Insights

Two novel NOTCH3 gene mutations, R587C and C988Y, were identified in Korean families with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). These findings confirm NOTCH3 mutations cause CADASIL across diverse ethnicities.

Area of Science:

  • Genetics
  • Neurology
  • Vascular Biology

Background:

  • Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukencephalopathy (CADASIL) is a hereditary angiopathy caused by NOTCH3 gene mutations.
  • Known NOTCH3 mutations typically alter cysteine residues in epidermal growth factor (EGF)-like repeats, leading to gain or loss of cysteine.

Purpose of the Study:

  • To identify novel NOTCH3 mutations associated with CADASIL.
  • To investigate the role of these mutations in CADASIL pathogenesis in different ethnic groups.

Main Methods:

  • Genetic sequencing of the NOTCH3 gene in patients from two unrelated Korean families with clinical and MRI findings consistent with CADASIL.
  • Analysis of mutation impact on cysteine residue count within EGF-like repeats.

Main Results:

  • Two novel NOTCH3 mutations, R587C and C988Y, were identified.
  • Both mutations result in an odd number of cysteine residues in an EGF-like repeat.
  • Patients presented with characteristic MRI abnormalities of CADASIL.

Conclusions:

  • The identified mutations R587C and C988Y are associated with CADASIL.
  • NOTCH3 mutations contribute to CADASIL pathogenesis irrespective of ethnic background.
  • These findings expand the spectrum of NOTCH3 mutations linked to CADASIL.

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