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Robert B. Hufnagel, Robert A. Sisk, Saima Riazuddin, Zubair M. Ahmed; Blue Cone Monochromatism: Phenotype And Genotype Assessment In Three U.S. Families. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6663.
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Blue cone monochromatism (BCM) is an inherited X-linked disorder of cone photoreceptors caused by mutations that prevent expression of the tandem opsin genes, OPN1LW and OPN1MW, which encode the red and green opsin proteins, respectively. The predominant effect of these mutations is either (1) deletion of the locus control region (LCR), a critical 5’ cis-enhancer, or (2) recombination resulting in a single red and green opsin gene coupled with an inactivating mutation. Patients with BCM are unable to distinguish color and have associated visual acuity deficits, photophobia, nystagmus, and, in certain cases, macular atrophy. Here, we describe the clinical and genetic analysis of three families with BCM, LNG2-LNG4.
Patients were consented to participate in this IRB-approved study at Cincinnati Children’s Hospital. Diagnosis of BCM was obtained in the clinical practice of R.A.S. by inheritance pattern, clinical history, and full-field and S-cone electroretinography (ERG). DNA was extracted from blood samples obtained from participating affected individuals, parents, and unaffected siblings. Genomic segments harboring the OPN1LW and OPN1MW genes were PCR amplified using opsin exon- and LCR-specific primers and Sanger sequenced through the ABI 3730xl analyzer.
Families LNG2-4 are Caucasian and resided for many generations in southeastern Kentucky. The probands of LNG2-4 range in age from 10 to 34 years old. All three have moderate impairment in best corrected visual acuity and reduced central macular thickness with granular retinal pigmented epithelium (RPE). Families LNG2 and LNG3 have deletions that include the LCR and exon 1 of the OPN1LW gene. The opsin coding regions of family LNG4 are normal, and analysis of the genomic segment containing the LCR is still underway.
Genetic studies and associated phenotypes of three Kentucky families with BCM are described. All three families have similar geographic and ethnic origins and clinical manifestations, including thin foveae over granular RPE. Two families have deletions extending from the LCR through exon 1 of the OPN1LW gene. Monitoring these patients for possible progressive maculopathy will be important to compare with phenotypes described in other genetic studies, particularly those cases from this region.
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