Cone-rod dystrophy caused by a novel homozygous RPE65 mutation in Leber congenital amaurosis

Klin Monbl Augenheilkd. 2014 Apr;231(4):405-10. doi: 10.1055/s-0034-1368221. Epub 2014 Apr 25.

Abstract

Background: The aim of this study was to describe an unexpected phenotype in a family with Leber congenital amaurosis (LCA) due to a retinal pigment epithelium-specific protein 65 kDa (RPE65) homozygous mutation.

History and signs: We analyzed a family from Yemen in which 3 individuals were affected with LCA. Linkage analysis using markers flanking the known LCA genes was done, followed by direct sequencing of RPE65.

Therapy and outcome: Severe visual impairment and night blindness were observed during infancy. We observed photophobia only in the 8-year-old patient. The youngest affected had bilateral hyperopia of +3.50 and visual acuity of 1/60. The oldest two had visual acuity limited to hand movements in the right eye (OD) and counting fingers in the left eye (OS) for the oldest and of 5/60 OD, 6/60 OS for the other. They showed disc pallor, attenuated vessels, white flecks in the retina mid-periphery and bull's eye maculopathy. ERGs of the oldest child were completely unresponsive. Genomic sequencing identified a novel homozygous missense mutation, IVS2-3C>G, in the second RPE65 intron.

Conclusions: We identified a novel LCA-related homozygous RPE65 mutation associated with a severe clinical presentation including an early and severe cone dysfunction. This is in contrast with the presentation associated with other RPE65 mutations predominantly causing rod-cone dystrophy with residual visual function.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Child
  • Child, Preschool
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Leber Congenital Amaurosis / diagnosis*
  • Leber Congenital Amaurosis / genetics*
  • Male
  • Mutation / genetics
  • Pedigree
  • Polymorphism, Single Nucleotide / genetics
  • Retinitis Pigmentosa / diagnosis*
  • Retinitis Pigmentosa / genetics*
  • Yemen
  • cis-trans-Isomerases / genetics*

Substances

  • retinoid isomerohydrolase
  • cis-trans-Isomerases