NPHP1 and nephronophthisis: For instance, the common variant p.Arg830Trp in the AHI1 gene was found to significantly enhance the frequency of retinal disease in patients with NPHP1-associated nephronophthisis.44 The identification of such genetic modifiers, as well as of other factors able to influence the penetrance and expression of ciliary gene mutations, represents one of the biggest challenges of current research on ciliopathies, with significant implications for diagnosis, management and counselling of patients and their families.