Purchase this article with an account.
M. E. McClements, M. Neitz, A. T. Moore, D. M. Hunt; Bornholm Eye Disease Arises From a Specific Combination of Amino Acid Changes Encoded by Exon 3 of the L/M Cone Opsin Gene. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2609.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To determine the genetic cause of the early-onset, non-progressive, X-linked cone disorder Bornholm eye disease in which affected individuals are dichromatic and exhibit cone dysfunction.
Twelve protanopic and five deuteranopic patient samples with Bornholm eye disease were used in this investigation. Four families (A, B, C and D), one unrelated individual (F) and one sample from a previous study (MN, Young et al Archives of Ophthalmology 2004) comprised the protanopic samples. A single family (E), one unrelated individual (G) and one sample (BED) also from Young et al (2004) made up the deuteranopic samples. For families A, B, C, E and the samples MN and BED, exons 3 to 5 of the L and M opsin genes were amplified and the products cloned and sequenced. For the other samples only exon 3 was amplified, cloned and sequenced.
The L and M opsin genes from all samples except those from family D possess nucleotide changes which encode a set of amino acid substitutions consistently found in BED patients but which are rarely reported in other dichromats. These substitutions are at sites 153, 171, 174, 178 and 180 encoded by exon 3. The combination of LIAVA was found in families A, B, C, E and sample F, and LVAVA in families G, BED and MN. For family D, the mutation C203R was identified in exon 4, a mutation known to cause cone dysfunction and deuteranomoly (Winderickx et al Nature Genetics 1992).
The combination of amino acids LIAVA or LVAVA at sites 153, 171, 174, 178 and 180, respectively, appears to produce a non-functional L/M pigment, leading to cone dysfunction (Neitz et al Visual Neuroscience 2004). These combinations of residues are consistently found in BED patients and are present in the opsin gene located in either the first or second place in the opsin gene array, thereby accounting for the dichromacy.
This PDF is available to Subscribers Only