title: Bilateral macular atrophy in blue cone monochromacy (BCM) with loss of the locus control region (LCR) and part of the red pigment gene.
abstract: OBJECTIVE
  To describe unusual macular abnormalities in a family with blue cone monochromacy (BCM, or X-linked incomplete achromatopsia) and deletion of about 9.5 kb comprising part of the red pigment gene and the region upstream of the red pigment gene.
  
  
  METHODS
  The molecular structure of the red and green pigment genes and the locus control region (LCR) upstream of the red gene were studied for deletions, rearrangements and point mutations by Southern blot analysis and PCR. Four affected males (ages 33, 45, 51, and 59) and a carrier female (age 58) were examined by funduscopy and fluorescein angiography. Extensive color vision testing as well as rod and cone electroretinography (ERG) were performed on two of them.
  
  
  RESULTS
  Analysis showed that the 6 kb proximal red gene region, exon 1 and about 3.1 kb of intron 1 of the red gene are deleted in this family. Exons 2-6 of the red gene, all the exons of the green gene and the Tex 28 gene were present. Four affected males had bilateral macular changes, including three with overt atrophy. All had visual acuity of 20/200 and their color vision was typical for BCM, with the absence of long- and middle-wavelength sensitive cone function. The ERG showed normal rod responses, whereas the photopic cone and 30-Hz flicker responses were >95% reduced.
  
  
  CONCLUSIONS
  We report the unusual association between macular atrophy and BCM resulting from the loss of an approximately 9.5 kb region encompassing the LCR, proximal red gene promoter elements and exon 1 of the red gene. However, loss of the LCR and promoter is not sufficient to explain the phenotype since we have observed other BCM families with similar deletions who do not exhibit macular changes.
authors.affiliation: Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor, MI 48105, USA. ayyagari@umich.edu
authors.forename: R
authors.initials: R
authors.lastname: Ayyagari
authors.forename: L E
authors.initials: LE
authors.lastname: Kakuk
authors.forename: C L
authors.initials: CL
authors.lastname: Coats
authors.forename: E L
authors.initials: EL
authors.lastname: Bingham
authors.forename: Y
authors.initials: Y
authors.lastname: Toda
authors.forename: J
authors.initials: J
authors.lastname: Felius
authors.forename: P A
authors.initials: PA
authors.lastname: Sieving
mesh_terms: D000328:Adult; D015139:Blotting, Southern; D005091:Exons; D005260:Female; D006801:Humans; D019901:Locus Control Region; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010860:Pigments, Biological / Q000235:genetics*; D011401:Promoter Regions, Genetic; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D010860:Pigments, Biological