IFT80 mutations cause a novel complex ciliopathy phenotype with retinal degeneration

Ciliopathies, a growing pleotropic class of diseases due to mutations in genes that play an important role in primary cilia function. These highly conserved organelles are key to cell signaling. We now know, that mutations in one gene may lead to more than one ciliopathy phenotype and that one ciliopathy phenotype may be due to mutations in more than one gene. We studied the case of a female child with a novel ciliopathy phenotype and identified two novel mutations in the gene IFT80. Previously, mutations in IFT80 have been associated with a very narrow rib cage and failure of the lungs. Bone anomalies are also part of this IFT80‐condition but with no vision problems documented. Our case had none of the features known to be associated with IFT80 mutations and had retinal degeneration (RD). This work broadens the IFT80‐phenotype spectrum and also shows RD can be a feature of many ciliopathies. Novel IFT80 mutations (Lys408Glu and Lys306*) were identified in a patient with none of the features of Jeune syndrome (normal chest and pelvic x‐rays) but retinal degeneration and a phenotype otherwise reminiscent of OFD6 (molar tooth sight, brain hamartoma digit anomaly). The amino acids involved were highly conserved and predicted to lead to the loss of most on the C‐terminal domain on protein modeling. This expands the phenotype spectrum associated with IFT80 mutations.