Investigation of CEP290 genotype-phenotype correlations in a patient with retinitis pigmentosa, infertility, end-stage renal disease, and a novel mutation

摘要

Background: Mutations in CEP290 cause autosomal recessive conditions with a wide range of severity and the lack of strong genotype-phenotype data makes it difficult to provide accurate prognostic data to patients and families. Methods: A retrospective chart review was conducted on a patient with a clinical diagnosis of Senior-Loken Syndrome, molecularly confirmed biallelic nonsense mutations in CEP290,and a recent finding of infertility secondary to non-motile sperm. Results: Here we present the case of a patient with a long-standing diagnosis of Senior-Loken syndrome due to findings of early-onset retinitis pigmentosa and renal disease. This is a patient who has been followed by ophthalmology and genetics for over 20 years and so provides valuable information on the natural history of CEP290-related ciliopathies. Additionally, we consider how this patient's biallelic nonsense variants in CEP290 affect phenotype severity through nonsense-mediated alternative splicing and how understanding this process could lead to future therapeutic options. Conclusions: CEP290 mutations are associated with a variety of overlapping clinical phenotypes, some of which will become better understood as more patients with these conditions survive to reproductive age. Similarly, increased understanding of the molecular mechanisms that underlie differences in phenotype may provide avenues to consider in future therapies.