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Clinical spectrum in CADASIL family with a new mutation

Tomas Peisker1, Libor Musil, Martin Hrebicek

  • 1Department of Neurology, Third Faculty of Medicine, Charles University in Prague and University Hospital Kralovske Vinohrady, Prague, Czech Republic.

Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia
|September 13, 2013
PubMed

Insights

A new NOTCH3 mutation (p.G296C) in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) causes varied symptoms, including stroke and migraine. Vascular changes were observed in all carriers, even asymptomatic ones.

Area of Science:

  • Genetics
  • Neurology
  • Vascular Biology

Background:

  • Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) diagnosis is challenging due to variable clinical presentations.
  • The type of NOTCH3 mutation and other vascular risk factors contribute to this presentation variability.

Purpose of the Study:

  • To investigate the clinical spectrum associated with a novel NOTCH3 mutation (p.G296C) in a CADASIL family.
  • To determine the diagnostic utility of comprehensive clinical and genetic evaluations for novel CADASIL mutations.

Main Methods:

  • Genetic testing was performed on six family members.
  • Clinical, neuropsychological, cerebral MRI, Doppler sonography, fundoscopic examination, and fluorescent angiography were conducted.
  • A novel NOTCH3 mutation on exon 6 (p.G296C) was identified.

Main Results:

  • The CADASIL mutation was detected in four individuals, with three exhibiting symptoms.
  • Symptomatic individuals presented with stroke and migraine.
  • Vascular changes in cerebral and/or retinal arteries were present in all mutation carriers, including one asymptomatic individual.

Conclusions:

  • The novel NOTCH3 p.G296C mutation is associated with CADASIL.
  • Heterogeneous clinical presentations can occur even with the same mutation.
  • Vascular changes are a consistent finding in carriers, regardless of clinical manifestation.
Abstract

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