Which genetic mutation is commonly associated with CADASIL?

CADASIL, which stands for Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, is a genetic condition primarily caused by mutations in the NOTCH3 gene. This gene is located on chromosome 19 and plays a critical role in vascular smooth muscle cell function and in the regulation of blood vessel development and maintenance.

When mutations occur in NOTCH3, they typically lead to abnormal accumulation of the NOTCH3 protein, which is implicated in the degeneration of vascular smooth muscle cells in the brain. This degeneration contributes to the specific pathology seen in CADASIL, including the deterioration of small arteries and the resultant ischemic episodes, which manifest as strokes and cognitive decline.

The other listed genes are associated with different conditions and do not play a role in CADASIL. For example, SCN5A mutations are associated with certain arrhythmias, CACNA1C mutations are linked to conditions like Timothy syndrome, and mutations in the FUS gene are involved in some types of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Hence, the NOTCH3 gene is the correct answer as it is the primary gene implicated in CADASIL.