Phenotypic Variations in a Large Family with Dominant Optic Atrophy Related to a Novel OPA1 Deletion

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Purpose: deletion. Design: Retrospective, longitudinal cohort study of a family from the Western part of France. Participants: 10-kb deletion and 5 healthy controls. Methods: sequencing, multiplex ligation-dependent probe amplification, and copy number variations using single nucleotide polymorphism array identified the genetic variation causing DOA. The relatedness between the different family branches was analyzed by micro-satellite markers. Best-corrected visual acuity (BCVA), Lanthony D-15 desaturated color vision test, retinal nerve fiber layer (RNFL), and macular ganglion cell layer (GCL) thickness were recorded at 2 different time points for longitudinal analyses. Main Outcome Measures: Best-corrected visual acuity, RNFL and GCL thickness at first and follow-up examinations. Correlations between morphological and functional measurements. Results: exons 30 and 31. Ophthalmic examination revealed a consistent BCVAvariability, ranging from 0 (Snellen equivalent, 20/20) to 1.61 (20/815) logarithm of the minimum angle of resolution (logMAR), strongly correlated to RNFL and GCL thickness, but moderately with age and not with dyschromatopsia. Follow-up of individuals evidenced a significant BCVA loss with a median of 0.018 logMAR per year (0.18 logMAR per decade) and a temporal, superior, and inferior RNFL thickness loss of 1.13, 0.70, and 0.50 μm/yr, respectively, whereas the nasal quadrant did not evolve. Conclusion: deletion in this DOA family illustrates the critical importance of screening for large genomic rearrangements in DOA genes and confirms the high intrafamilial phenotypic variability while correlating BCVA with RNFL and GCL thickness. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.