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CADASIL with a novel NOTCH3 mutation (Cys478Tyr)

Kokoro Ozaki1, Takashi Irioka2, Kinya Ishikawa1

  • 1Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association
|January 18, 2015
PubMed

Insights

This study identifies a novel NOTCH3 gene mutation in a Japanese family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Early genetic testing is recommended for patients with characteristic MRI findings, even with mild symptoms like chronic headaches.

Area of Science:

  • Neurology
  • Genetics
  • Vascular Biology

Background:

  • Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disease.
  • NOTCH3 gene mutations are increasingly recognized as a cause of CADASIL.
  • Early diagnosis and understanding the genetic basis are crucial for managing CADASIL.

Observation:

  • Two patients from a Japanese family presented with mild clinical symptoms, including chronic headache and a history of minor stroke.
  • Distinctive magnetic resonance imaging (MRI) features were observed, suggestive of CADASIL.
  • A novel heterozygous NOTCH3 mutation (p.Cys478Tyr) was identified in both patients, resulting in cysteine loss.

Findings:

  • The identified NOTCH3 mutation, p.Cys478Tyr, is a new cause of CADASIL.
  • The mutation leads to a loss of a critical cysteine residue in the NOTCH3 protein.
  • Clinical presentation can be mild, even with a confirmed NOTCH3 mutation.

Implications:

  • Genetic testing for NOTCH3 mutations should be considered in patients with suggestive MRI findings, regardless of symptom severity.
  • This discovery broadens the known spectrum of NOTCH3 mutations associated with CADASIL.
  • Further research into the genotype-phenotype correlation in CADASIL is warranted.

Keywords:
C478YCADASILCys478TyrNOTCH3cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathymutation

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