First report of a p.Cys484Tyr Notch3 mutation in a CADASIL patient with acute bilateral multiple subcortical...

Area of Science:

• Neurology
• Genetics
• Vascular Biology

Background:

• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic small vessel disease.
• NOTCH3 gene mutations are the primary cause, with common hotspots, but exon 9 mutations are rare.
• The p.C484T mutation has not been previously reported in CADASIL cases.

Observation:

• A Chinese female patient presented with acute bilateral multiple subcortical infarcts, an unusual manifestation of CADASIL.
• Genetic analysis revealed a novel Cys484Tyr mutation in exon 9 of the NOTCH3 gene.
• This newly identified mutation was also present in the patient's two daughters, indicating familial inheritance.

Findings:

• The patient's condition was attributed to hemodynamic changes and hypercoagulability.
• The discovery of the Cys484Tyr mutation expands the known spectrum of NOTCH3 mutations associated with CADASIL.
• This case highlights a rare presentation of acute bilateral subcortical infarcts in CADASIL.

Implications:

• This finding broadens the understanding of NOTCH3 mutation variability in CADASIL.
• It provides insights into the mechanisms underlying acute bilateral subcortical infarcts in CADASIL patients.
• Recommendations for early intervention, diagnosis, and treatment strategies for similar cases can be developed.