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

Blue cone monochromacy (BCM) is an X-linked ocular disease characterized by poor visual acuity, nystagmus, and photodysphoria in males with severely r educed color discriminatisn. Deletions, rearrangements and point mutations in the I ed and green pigment genes have been implicated in causing BCM. We assessed the spectrum of genetic alternations 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 ophthalmo logical examination. All families showed clinical features associated with BCM. Acuities were reduced in all affected males. and photopic b-wave was r educed by more than 90% in seven families. In three families, however, the photopic b-wave response showed uncharacteristic relative preservation of 3 0-80% (of the clinical low-normal value). The color vision was unusually pr eserved in two affected males, but this was not correlated with photopic el ectroretinography retention. Progressive macular atrophy was observed in af fected 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 showe d a range of deletions from the loss of a single exon to loss of the comple te red gene. In one family no mutation was found in the exons of the red ge ne or the locus control region but showed loss of the complete green gene. No association was observed between the phenotypes and genotypes in these f amilies.