[A new Spanish family with CADASIL associated with 346C>T mutation of NOTCH3 gene]

Area of Science:

• Neurology
• Genetics
• Vascular Neurology

Background:

• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare, inherited adult-onset cerebrovascular disorder.
• It is characterized by migraine, recurrent ischemic strokes, subcortical dementia, and characteristic white matter changes on MRI.
• Mutations in the NOTCH3 gene are the primary cause of CADASIL.

Observation:

• This report details two affected individuals from a Spanish family presenting with clinical and neuroimaging findings consistent with CADASIL.
• Diagnostic evaluation included neuroimaging, which revealed typical white matter abnormalities and subcortical infarcts.
• Skin biopsy results were negative for the characteristic granular osmiophilic material.

Findings:

• Genetic analysis confirmed the presence of the 346C>T mutation in exon 3 of the NOTCH3 gene in both affected family members.
• This specific mutation in the NOTCH3 gene is a frequent cause of CADASIL in European populations.
• This represents the first reported Spanish family with CADASIL linked to this particular NOTCH3 gene mutation.

Implications:

• This finding expands the known genetic landscape of CADASIL in Spain.
• It highlights the importance of genetic testing for the NOTCH3 gene in suspected cases, even with negative skin biopsies.
• Further research into the prevalence of this mutation in the Spanish population is warranted.