Mutational screening of NOTCH3 gene reveals two novel mutations: complexity of CADASIL diagnosis

Area of Science:

• Neurology
• Genetics
• Vascular Biology

Background:

• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary adult-onset vascular disease.
• Characterized by progressive neurological deficits including strokes and dementia, CADASIL impacts quality of life.
• The disease is caused by mutations in the NOTCH3 gene, often affecting cysteine residues in extracellular domains.

Purpose of the Study:

• To identify novel mutations in the NOTCH3 gene associated with CADASIL.
• To provide clinical descriptions of affected individuals and their relatives.
• To underscore the importance of comprehensive NOTCH3 gene analysis for CADASIL diagnosis.

Main Methods:

• Direct sequencing of exons 2-23 of the NOTCH3 gene was performed.
• Mutation analysis focused on regions encoding EGF-like domains.
• Genetic counseling was provided to patients pre- and post-testing.

Main Results:

• Two novel NOTCH3 gene mutations were identified in exons 6 and 15.
• Clinical data for probands and available family members were documented.
• The findings contribute to the mutational spectrum of CADASIL.

Conclusions:

• Novel NOTCH3 mutations expand the known genetic causes of CADASIL.
• Comprehensive NOTCH3 gene analysis is crucial for diagnosing suspected cases.
• Further reporting of cases is essential for understanding CADASIL incidence and prevalence.