Spectrum of color gene deletions and phenotype in patients with blue cone monochromacy

Hum Genet. 2000 Jul;107(1):75-82. doi: 10.1007/s004390000338.

Abstract

Blue cone monochromacy (BCM) is an X-linked ocular disease characterized by poor visual acuity, nystagmus, and photodysphoria in males with severely reduced color discrimination. Deletions, rearrangements and point mutations in the red and green pigment genes have been implicated in causing BCM. We assessed the spectrum of genetic alterations in ten families with BCM by Southern blot, polymerase chain reaction, and sequencing analysis, and the phenotype was characterized by ophthalmoscopy, fluorescein angiography, and a battery of tests to assess color vision in addition to routine ophthalmological examination. All families showed clinical features associated with BCM. Acuities were reduced in all affected males, and photopic b-wave was reduced by more than 90% in seven families. In three families, however, the photopic b-wave response showed uncharacteristic relative preservation of 30-80% (of the clinical low-normal value). The color vision was unusually preserved in two affected males, but this was not correlated with photopic electroretinography retention. Progressive macular atrophy was observed in affected members of two BCM families while the rest of the families presented with normal fundus. In nine families deletions were identified in the gene encoding the red-sensitive photopigment and/or in the region up to 17.8 kb upstream of the red gene which contains the locus control region and other regulatory sequences. In the same nine families the red pigment gene showed a range of deletions from the loss of a single exon to loss of the complete red gene. In one family no mutation was found in the exons of the red gene or the locus control region but showed loss of the complete green gene. No association was observed between the phenotypes and genotypes in these families.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Blotting, Southern
  • Child, Preschool
  • Contig Mapping
  • DNA Mutational Analysis
  • Exons
  • Female
  • Fluorescein Angiography
  • Gene Deletion*
  • Genetic Linkage*
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Models, Genetic
  • Ophthalmoscopy
  • Phenotype
  • Polymerase Chain Reaction
  • Retinal Cone Photoreceptor Cells / pathology*
  • Retinal Cone Photoreceptor Cells / ultrastructure
  • Retinal Diseases / genetics*
  • Retinal Diseases / pathology
  • Vision, Ocular / genetics
  • X Chromosome / genetics*