CEP290 and retinal degeneration: These observations provided a hypothesis that may explain why some NPHP genes with null mutations (such as NPHP3, CEP290, and RPGRIP1L) present as severe congenital-onset dysplasia and malformation in multiple organs including the kidney, brain and eye while hypomorphic mutations in the same genes produce milder phenotypes, which include late-onset degeneration and fibrosis leading to NPHP in the kidney and retinal degeneration in the eye.