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T. Desronvil, D. Cestari, J. F. Rizzo, S. Lessell, J. L. Wiggs; OPA1 Mutations in a US Clinic-Based Population of Optic Atrophy Patients. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3074.
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© ARVO (1962-2015); The Authors (2016-present)
OPA1 mutations are currently the most common cause of inherited optic atrophy. Previous population screening studies, performed primarily in European populations, have identified OPA1 mutations in 30-70% of patients with inherited optic atrophy, with the highest prevalence in Denmark (approximately 1/10,000). The purpose of this study is to determine the prevalence of OPA1 mutations in a US clinic-based population of patients with optic atrophy.
Twenty consecutive patients were ascertained through the Neuro-ophthalmology service at the Massachusetts Eye and Ear Infirmary. The majority of patients (17/20) were sporadic without a known family history of optic atrophy. All patients underwent a complete ocular examination including visual acuity and color vision testing, funduscopic examination of the optic nerve and automated visual field testing. Genomic DNA was purified from mouthwash samples and all 28 OPA1 exons and flanking introns (OPA1 transcript variant 8, NM_130837.1) were directly sequenced using the ABI3100 genetic analyzer and BIGDYE chemistries. Sequence data was analyzed using the contig function of Vector NTI.
OPA1 mutations were identified in 6/20 patients, including 3 novel mutations (Thr472del_ta; Asn700ins_t; Val882del_g). All of the novel mutations were small insertion/deletions that created a downstream premature stop codon. In addition to these 6 patients, 8 patients have a probable whole or partial gene deletion based on apparent allelic homozygosity of a selection of 20 common SNPs distributed throughout the gene. An OPA1 mutation was not found in 6 patients. The OPA1 mutation carriers did not have significantly different clinical findings when compared to those patients without OPA1 mutations. Five of the six OPA1 mutation carriers and 7/8 probable OPA1 deletion patients did not have a family history of optic atrophy.
The results of this study suggest that OPA1 mutations are a common cause of optic atrophy in the United States, and that optic atrophy patients should be screened for OPA1 mutations even in the absence of a family history of the disease.
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