Dominant optic atrophy: Refining the clinical diagnostic criteria in light of genetic linkage studies1☆,
Section snippets
Clinical
Nine families with DOA were identified in the United Kingdom. The study had been approved by the ethical committee of Guy’s and St. Thomas’ Hospital. All family members were visited at home and questioned regarding the onset of visual loss, its progression, and their perception of visual handicap. The home examination comprised best-corrected Snellen visual acuity, color vision testing using Ishihara and Hardy Richter Rand (HRR) plates, confrontation field testing using a red target, and optic
Linkage and haplotype analysis
When two-point linkage analysis was performed for each marker in each family, although positive total lod scores were obtained with all markers, family 2 consistently had negative values.19 The multipoint lod scores across all the 12 markers used from this region of chromosome 3q for each family are given in Table 1. The combined lod score of 10.73 suggests linkage of DOA in eight of our pedigrees to the 3q27–3q29 region, while family 2 appears to have a variant of DOA not linked to this region
Discussion
In our study using genotyping as a method of confirming affected individuals in families with DOA, we have been able to clarify the natural history and identify the minimum clinical diagnostic criteria for the condition. The latter are evidence of temporal or diffuse optic disc pallor and any color vision defect in an individual from a pedigree in which DOA is known to be segregating, even if the visual acuity is normal. Optic disc pallor is the most important clinical sign in differentiating
Acknowledgements
The authors thank the Iris Fund for Prevention of Blindness who funded this study.
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Genotype-phenotype and OCT correlations in Autosomal Dominant Optic Atrophy related to OPA1 gene mutations: Report of 13 Italian families
2017, Journal of the Neurological SciencesCitation Excerpt :While initial studies demonstrated only a blue defect in ADOA [25,33], a mixed colour vision defect has been reported as the most common in successive reports [32,34], with a percentage similar to our population [35]. Previous studies have shown that optic disc atrophy was a very sensitive indicator of disease, being found in a high percentage of affected patients [23–25,32,34]. Similarly, we found temporal pallor to subatrophy or complete atrophy in 68% of subjects, but none of our patients showed pallor of the nasal segment, differently from what observed by Poumila and colleagues [23].
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2010, Journal of the Neurological SciencesAutosomal Dominant Optic Atrophy: Penetrance and Expressivity in Patients With OPA1 Mutations
2007, American Journal of OphthalmologyCitation Excerpt :In our cohort, 29% of mutation carriers had normal optic disks. Previously, this has been the most important feature distinguishing nonaffected individuals from mildly affected carriers.6,25 This may be due to the large variation in age of patients examined, and again, it may be hypothesized that with time, these mutation carriers may develop optic disk changes.
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Supported by the Iris Fund for Prevention of Blindness, London, England.
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None of the authors has any financial interest relating to this article.