Purchase this article with an account.
Eric Gaier, Phillip Skidd, Maria Janessian, Simmons Lessell, Dean Cestari, Joseph Rizzo, Janey Wiggs; Clinical features of OPA1-related optic neuropathy: a retrospective case series. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1355.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Dominant optic atrophy (DOA) is the most common hereditary optic neuropathy. The most common form of DOA, DOA type 1 (Kjer’s disease) accounts for 40-60% of cases and is associated with mutation of the OPA1 gene. Previously, clinical studies focusing on OPA1 mutations have been limited to a few mutations and clinical parameters. In the present study, we evaluated and analyzed detailed clinical information for patients referred to a major tertiary care center for OPA1 testing for suspected DOA.
In this retrospective case series, we review the clinical records of 62 patients referred for PCR-based sequencing of OPA1. Missense and small deletions/insertions found by sequencing were compared with those reported in the literature, and objective analyses were used to determine the likelihood of pathogenicity for specific DNA changes. A subset of patients was selected for Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The clinical features examined include, but are not limited to, visual acuity, Ishihara testing, automated visual field testing, and dilated fundoscopy.
Clinical data was available for 54 patients (31 male; 23 female). The majority (28/41; 68.3%) were referred by an optometrist/ophthalmologist for a problem related to optic nerve appearance. Of the 62 patients that underwent diagnostic OPA1 sequencing, 18 (29.0%) were found to have potentially disease-causing coding mutations: 3 splice site mutations, 3 missense mutations, and 12 nonsense/truncating mutations. The common TTAG deletion comprised 7 of the 12 nonsense mutations in 4 unrelated families, confirming previous reports of this mutation hot spot. Three sequence mutations are novel. MLPA analysis identified 5 patients with large-scale deletions/duplications unrecognized by sequencing. Deletion spans ranged from 3 exons to the entire gene. Automated visual field testing was the most sensitive measure of disease status as assessed in a subset of individuals followed over 1-5 years.
Our results show that OPA1 mutations are a common cause of optic neuropathy in the tertiary referral setting and large-scale genomic aberrations account for a small subset of OPA1-related neuropathies. Automated visual field testing may be the best measure of disease progression in these patients.
This PDF is available to Subscribers Only