Gardner, JC;
Michaelides, M;
Holder, GE;
Kanuga, N;
Webb, TR;
Mollon, JD;
Moore, AT;
(2009)
Blue cone monochromacy: Causative mutations and associated phenotypes.
Molecular Vision
, 15
(90-93)
876 - 884.
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Abstract
Purpose: To perform a phenotypic assessment of members of three British families with blue cone monochromatism (BCM), and to determine the underlying molecular genetic basis of disease.Methods: Affected members of three British families with BCM were examined clinically and underwent detailed electrophysiological and psychophysical testing. Blood samples were taken for DNA extraction. Molecular analysis involved the amplification of the coding regions of the long (L) and medium (M) wave cone opsin genes and the upstream locus control region (LCR) by polymerase chain reaction (PCR). Gene products were directly sequenced and analyzed.Results: In all three families, genetic analysis identified that the underlying cause of BCM involved an unequal crossover within the opsin gene array, with an inactivating mutation. Family 1 had a single 5'-L-M-3' hybrid gene, with an inactivating Cys203Arg (C203R) mutation. Family 3 had an array composed of a C203R inactivated 5'-L-M-3' hybrid gene followed by a second inactive gene. Families 1 and 3 had typical clinical, electrophysiological, and psychophysical findings consistent with stationary BCM. A novel mutation was detected in Family 2 that had a single hybrid gene lacking exon 2. This family presented clinical and psychophysical evidence of a slowly progressive phenotype.Conclusions: Two of the BCM- causing family genotypes identified in this study comprised different hybrid genes, each of which contained the commonly described C203R inactivating mutation. The genotype in the family with evidence of a slowly progressive phenotype represents a novel BCM mutation. The deleted exon 2 in this family is not predicted to result in a shift in the reading frame, therefore we hypothesize that an abnormal opsin protein product may accumulate and lead to cone cell loss over time. This is the first report of slow progression associated with this class of mutation in the L or M opsin genes in BCM.
Type: | Article |
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Title: | Blue cone monochromacy: Causative mutations and associated phenotypes |
Open access status: | An open access version is available from UCL Discovery |
Publisher version: | http://www.molvis.org/molvis/v15/a91/ |
Language: | English |
Additional information: | This work is licensed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivativeWorks 3.0 license. You are free to share (copy, distribute and transmit the work), but you must attribute the author, you may not use this work for commercial purposes and you may not alter, transform, or build upon this work and distribute any derivative works you create under a similar license. |
Keywords: | Human color-vision, molecular-genetics, genes, green, discrimination, expression, locus, red |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
URI: | https://discovery.ucl.ac.uk/id/eprint/140999 |
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