We analyzed sequential pathology in a mouse model of XLAS harboring a human nonsense mutation of COL4A5. In mutant mice, nephropathy commenced from focal GBM irregularity by EM at 6 weeks of age, prior to exclusive crescents at 13 weeks of age. Here, COL4A5 is linked to X-linked hydrocephalus with stenosis of the aqueduct of Sylvius.