Clinical Characterization of 66 Patients With Congenital Retinal Disease Due to the Deep-Intronic c.2991+1655A>G Mutation in CEP290

Invest Ophthalmol Vis Sci. 2018 Sep 4;59(11):4384-4391. doi: 10.1167/iovs.18-24817.


Purpose: To describe the phenotypic spectrum of retinal disease caused by the c.2991+1655A>G mutation in CEP290 and to compare disease severity between homozygous and compound heterozygous patients.

Methods: Medical records were reviewed for best-corrected visual acuity (BCVA), age of onset, fundoscopy descriptions. Foveal outer nuclear layer (ONL) and ellipsoid zone (EZ) presence was assessed using spectral-domain optical coherence tomography (SD-OCT). Differences between compound heterozygous and homozygous patients were analyzed based on visual performance and visual development.

Results: A total of 66 patients were included. The majority of patients had either light perception or no light perception. In the remaining group of 14 patients, median BCVA was 20/195 Snellen (0.99 LogMAR; range 0.12-1.90) for the right eye, and 20/148 Snellen (0.87 LogMAR; range 0.22-1.90) for the left. Homozygous patients tended to be more likely to develop light perception compared to more severely affected compound heterozygous patients (P = 0.080) and are more likely to improve from no light perception to light perception (P = 0.022) before the age of 6 years. OCT data were available in 12 patients, 11 of whom had retained foveal ONL and EZ integrity up to 48 years (median 23 years) of age.

Conclusions: Homozygous patients seem less severely affected compared to their compound-heterozygous peers. Improvement of visual function may occur in the early years of life, suggesting a time window for therapeutic intervention up to the approximate age of 17 years. This period may be extended by an intact foveal ONL and EZ on OCT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, Neoplasm / genetics*
  • Cell Cycle Proteins
  • Child
  • Child, Preschool
  • Cytoskeletal Proteins
  • Electroretinography
  • Female
  • Follow-Up Studies
  • Gene Amplification
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Introns / genetics*
  • Leber Congenital Amaurosis / diagnosis*
  • Leber Congenital Amaurosis / genetics*
  • Leber Congenital Amaurosis / physiopathology
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Polymerase Chain Reaction
  • Retina / diagnostic imaging
  • Retina / physiopathology
  • Retrospective Studies
  • Tomography, Optical Coherence
  • Visual Acuity / physiology
  • Young Adult


  • Antigens, Neoplasm
  • Cell Cycle Proteins
  • Cep290 protein, human
  • Cytoskeletal Proteins
  • Neoplasm Proteins