Blue cone monochromatism: clinical findings in patients with mutations in the red/green opsin gene cluster

Background: X-linked blue cone monochromatism (BCM) has to be differentiated from x-linked cone dystrophy and autosomal recessive rod monochromatism. Methods: In nine male patients with congenital cone dysfunction (one family, six single cases; age range: 955 years), mutations in the red/green opsin gene cluster were confirmed. Clinical findings were analyzed retrospectively. Results: In one family and three single cases, a single red-green hybrid gene was found carrying a Cys203Arg mutation. Two patients had multiple opsin genes, a red/ green hybrid gene and at least one green pigment gene, all carrying the Cys203Arg mutation. In one patient, a large deletion of the locus control region and parts of the red pigment gene were detected. Two patients (ages: 45 and 55 years) complained about progression. Two patients presented with nystagmus. Refractive errors (+8.0 and -11.0 D) and visual acuity were variable (0.05-0.3). Only four patients had a visual acuity greater than or equal to0.1. In two patients, visual acuity could be improved using blue filter glasses. Four of five patients greater than or equal to25 years had dystrophic alterations in the macula. Severe color vision defects and relative central scotoma were present in all patients. In the electroretinogram, residual cone responses were detected in 2/8 patients. Conclusions: Hybrid red/green opsin genes carrying the Cys203Arg mutation are a frequent cause of BCM in German patients. Molecular genetic evaluation is mandatory for adequate diagnosis of patients since from the clinical data only two patients were diagnosed as having BCM. In the other patients, either rod monochromatism or cone-rod dystrophy could not be excluded with certainty. The patients should be cautioned that macular dystrophy may develop in adults older than 30 years.