Missense Variants in COL4A1/2 Are Associated with Cerebral Aneurysms: A Case Report and Literature Review.

ABSTRACT

BACKGROUND: Although cerebral aneurysm (CA) is a defining complication of COL4A1/2-related vasculopathy, the specific factors influencing its onset remain uncertain. This study aimed to identify and analyze these factors. METHODS: We described a family presenting with a novel variant of the COL4A1 gene complicated with CA. Concurrently, an exhaustive review of previously documented patients with COL4A1/2-related vasculopathy was conducted by sourcing data from PubMed, Web of Science, Google Scholar, and Ichushi databases. We compared the variant types and locations between patients with CA (positive group) and those without CA (negative group). RESULTS: This study included 53 COL4A1/2 variants from 76 patients. Except for one start codon variant, all the identified variants in CA were missense variants. Otherwise, CA was not associated with other clinical manifestations, such as small-vessel disease or other large-vessel abnormalities. A higher frequency of missense variants (95.5% vs. 58.1%, p = 0.0035) was identified in the CA-positive group. CONCLUSIONS: CA development appears to necessitate qualitative alterations in COL4A1/2, and the underlying mechanism seems independent of small-vessel disease or other large-vessel anomalies. Our findings suggest that a meticulous evaluation of CA is necessary when missense variants in COL4A1/2 are identified.