In the second family, the two affected siblings were homozygous for the missense variant c.145C<G, p.(Pro49Ala) of COL3A1 and showed cobblestone-like cortical malformation, cerebellar cysts, and white matter abnormalities, developmental delay, and seizures.
Further studies demonstrated that Col3a1 null mutant mice exhibit overmigration of neurons beyond the pial basement membrane and a cobblestone-like cortical malformation similar to the phenotype seen in Gpr56 null mutant mice.