Bi-allelic variants in COL3A1 encoding the ligand to GPR56 are associated with cobblestone-like cortical malformation, white matter changes and cerebellar cysts

Collagens are important constituents of connective tissue but are also present in the membrane lining the surface of the brain. The COL3A1 gene encodes the chains of type III procollagen. Mutation of one copy of this gene results in vascular Ehlers Danlos syndrome (EDS), a connective tissue disorder. We now have discovered that mutations of both copies of this gene, so-called bi-allelic mutations, result in a complex brain malformation with or without signs of vascular EDS. This brain malformation is very similar to that associated with mutations in the gene encoding the receptor of type III collagen, G protein-coupled receptor 56 (GPR56), also known as Adhesion G protein-coupled Receptor G1 (ADGRG1). (By Prof. Anna Jansen, )