Zebrafish col4a1 loss-of-function models mirror key neurovascular and ocular features of COL4A1/A2 syndrome and enable human variants assessment in vivo.

ABSTRACT: Pathogenic variants in COL4A1 and COL4A2, encoding type IV collagen α1 and α2 chains-core components of all basement membranes-cause a multisystem disorder with variable expressivity. Affected individuals commonly present with cerebral small vessel disease (cSVD), unmanageable intracerebral haemorrhage (ICH), drug-resistant epilepsy, microphthalmia, and congenital cataract. Severe phenotypes are often linked to glycine substitutions that disrupt α1/α2 heterotrimer assembly, though insertions, deletions, and haploinsufficiency seem to also be pathogenic. Limited insight into collagen IV α1 and α2 biology and how specific variants affect their functions-coupled with a lack of rapid in vivo assays for functional variants classification-hampers patient stratification and therapy development. H

SUBMITTER: Paradisi G 

PROVIDER: S-EPMC12835968 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature