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Ajoy Vincent, Matteo DiScipio, Erika Tavares, Nicole Roslin, Elise Heon; A Novel Autosomal Dominant Retinal Dystrophy: Phenotypic description and Preliminary Genetic Investigations in a Pedigree.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5050. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To describe the clinical phenotype in a peculiar retinal dystrophy predominantly affecting the posterior pole in a pedigree.
Fourteen members (3 – 70 years of age; including five affected) of a large European pedigree were recruited. All members underwent detailed ophthalmological examination including best corrected visual acuity, color vision, contrast sensitivity and fundus examination. Spectral-domain optical coherence tomography (SD-OCT), fundus auto-fluorescence testing (FAF) and full-field electroretinography (ERG) were performed in three affected individuals. Panel based genetic testing for known retinal dystrophy genes (n = 244) was performed using a CLIA certified lab in proband’s mom. DNA was extracted from blood or saliva in all family members. Linkage analysis was performed using data generated from single nucleotide polymorphism (SNP) BeadChip using Omni5Exome kit (Illumina).
The best corrected visual acuity ranged between 20/20 and 20/300 in all patients. Mild red-green color vision deficit was noted in the oldest affected individual (67 years of age). Fundus examination showed confluent hypo-pigmented deep retinal changes, and retinal atrophy within the posterior pole; macular atrophy was noted in older affected individuals (64 and 67 years, respectively). The FAF testing showed a speckled pattern (hyper and hypo) of auto-fluorescence within the posterior pole in all affected eyes that were tested (n = 3); large atrophic patches were noted in older affected individuals. Macular SD-OCT scans showed numerous, small, hyper-reflective depositions at the level of the pigment epithelium in the proband (24 years); the older affected individuals demonstrated marked disruption of photoreceptor inner and outer segments within the macula. The ERG was normal to all tested stimuli in the proband; the photopic ERG responses were borderline in the older affected individuals. Panel based genetic testing results returned negative. Linkage analysis showed a maximum LOD score of 1.79 under a dominant model of inheritance assuming 99% penetrance and 0.001 disease allele frequency; 11 linked regions spanning 3.3% of the genome was identified.
The clinical phenotype described in this study appears novel and likely represents a slowly progressive retinal dystrophy affecting the posterior pole. The underlying genetic basis remains to be elucidated
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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