We describe a family with severe congenital retinal degeneration (LCA), Joubert syndrome and massively enlarged polycystic kidneys. It results from a homozygous missense mutation in POC1B, a gene essential for ciliogenesis, basal body and centrosome integrity. Knockdown in zebrafish evokes a corresponding ocular-renal phenotype. In view of simultaneous studies reporting mutations in non-syndromic cone-rod dystrophy, our findings suggest that POC1B mutations may cause retinal ciliopathies of variable severity.