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Alison J. Hardcastle, Jessica C. Gardner, Yinghua Quan, Andrew Stockman, Graham E. Holder, Naheed Kanuga, Tom R. Webb, Anthony T. Moore, Michel Michaelides; Mutation Analysis Of The OPN1LW And OPN1MW Cone Opsin Genes In A Cohort Of British Families With Blue Cone Monochromacy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5386.
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To determine the underlying molecular cause of Blue Cone Monochromacy (BCM) in British families and correlate genotype with phenotype.
Molecular analysis involved amplification of the coding regions of the OPN1LW and OPN1MW cone opsin genes and their promoters and upstream locus control region (LCR) by polymerase chain reaction. Gene products were directly sequenced and analysed. Detailed electrophysiological and psychophysical testing are currently being performed.
We have identified ‘one-step’ LCR deletions in 3 families which vary in extent. In another family, the entire opsin array was found to be deleted. The extent of the deletion was defined and flanking genes (MECP2 and TKTL1) were found to be present. We also identified 3 families who have a ‘two-step’ mutation mechanism leading to a single 5’L-M3’ hybrid gene with an inactivating C203R mutation in exon 4.
This is the first time LCR deletions have been identified in British BCM patients, confirming that this ‘one-step’ mechanism is a common cause of BCM. Interestingly another patient was deleted for the entire opsin array; at present BCM is the only phenotype observed in this patient. The previously described inactivation mutation (C203R) was found in 3 different hybrid genes, again confirming that this is a common cause of BCM. Loss of colour discrimination and visual acuity in BCM is severe but usually stationary, with progression reported in a small number of cases. Follow up phenotyping studies of the genotyped families are underway to assess for signs of progression.
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