Ocular manifestations of the genetic renal tubulopathies

Background: The genetic tubulopathies are rare and heterogenous disorders that are often difficult to identify. This study examined the tubulopathy-causing genes for ocular associations that suggested their genetic basis and, in some cases, the affected gene. Methods: Sixty-seven genes from the Genomics England renal tubulopathy panel were reviewed for ocular features, and for retinal expression in the Human Protein Atlas and an ocular phenotype in mouse models in the Mouse Genome Informatics database. The genes resulted in disease affecting the proximal tubules (n = 24); the thick ascending limb of the loop of Henle (n = 10); the distal convoluted tubule (n = 15); or the collecting duct (n = 18). Results: Twenty-five of the tubulopathy-associated genes (37%) had ocular features reported in human disease, 49 (73%) were expressed in the retina, although often at low levels, and 16 (24%) of the corresponding mouse models had an ocular phenotype. Ocular abnormalities were more common in genes affected in the proximal tubulopathies (17/24, 71%) than elsewhere (7/43, 16%). They included structural features (coloboma, microphthalmia); refractive errors (myopia, astigmatism); crystal deposition (in oxalosis, cystinosis) and sclerochoroidal calcification (in Bartter, Gitelman syndromes). Retinal atrophy was common in the mitochondrial-associated tubulopathies. Structural abnormalities and crystal deposition were present from childhood, but sclerochoroidal calcification typically occurred after middle age. Conclusions: Ocular abnormalities are uncommon in the genetic tubulopathies but may be helpful in recognizing the underlying genetic disease. The retinal expression and mouse phenotype data suggest that further ocular associations may become apparent with additional reports. Early identification may be necessary to monitor and treat visual complications.