COL4A1 and COL4A2 Gene Duplication or Triplication as a Genetic Cause of Cerebral Small Vessel Disease in Adults

This large series confirms the pathogenicity of COL4A1/2 duplications and triplications in adult-onset CSVD. Phenotypic variability likely reflects differences in duplication/triplication size, gene content, and modifying factors. Our findings highlight a distinct cerebral-only phenotype linked to gene dosage-related overexpression and underscore the importance of screening for copy number variations in patients with otherwise unexplained cerebral microangiopathy, even in the absence of a family history.