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The Prevalence and Natural History of Dominant Optic Atrophy Due to OPA1 Mutations

Lookup NU author(s): Dr Patrick Yu Wai Man, Philip Griffiths, Dr Ailbhe Burke, Michael Clarke, Professor Gavin Hudson, Professor Robert Taylor, Professor Rita HorvathORCiD, Professor Patrick Chinnery


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Purpose: Autosomal dominant optic atrophy (DOA) is a major cause of visual impairment in young adults that is characterized by selective retinal ganglion cell loss. To define the prevalence and natural history of this optic nerve disorder, we performed a population-based epidemiologic and molecular study of presumed DOA cases in the north of England. Design: Case series. Participants: Seventy-six affected probands with a clinical diagnosis of DOA were identified from our neuro-ophthalmology and neurogenetics database. Methods: OPA1 genetic testing was performed using a polymerase chain reaction-based sequencing strategy. OPA1-negative cases were then screened for large-scale OPA1 rearrangements and OPA3 mutations. Additional affected family members identified through contact tracing were examined, and longitudinal visual data were analyzed. Main Outcome Measures: The prevalence and molecular characteristics of DOA in the north of England. Visual function and disease progression among patients with OPA1-positive mutations. Results: The detection rate of OPA1 mutations was 57.6% among probands with a positive family history of optic atrophy (19/33) and 14.0% among singleton cases (6/43). Approximately two thirds of our families with DOA harbored OPA1 mutations (14/22, 63.6%), and 5 novel OPA1 mutations were identified. Only 1 family carried a large-scale OPA1 rearrangement, and no OPA3 mutations were found in our optic atrophy cohort. The minimum point prevalence of DOA in the north of England was 2.87 per 100 000 (95% confidence interval [CI], 2.54-3.20), or 2.09 per 100 000 (95% CI, 1.95-2.23) when only OPA1-positive cases were considered. Snellen visual acuity varied markedly between OPA1-positive cases with a mean of 20/173 (range 20/20 to hand movements), and visual function worsened in 67.4% of patients during follow-up. The mean rate of visual loss was 0.032 logarithm of the minimum angle of resolution per year, but some patients experienced faster visual decline (range = 0-0.171 logarithm of the minimum angle of resolution/year). OPA1 missense mutations were associated with a significantly worse visual outcome compared with other mutational subtypes (P=0.0001). Conclusions: Dominant optic atrophy causes significant visual morbidity and affects at least 1 in 35 000 of the general population. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2010; 117: 1538-1546 (C) 2010 by the American Academy of Ophthalmology.

Publication metadata

Author(s): Yu-Wai-Man P, Griffiths PG, Burke A, Sellar PW, Clarke MP, Gnanaraj L, Ah-Kine D, Hudson G, Czermin B, Taylor RW, Horvath R, Chinnery PF

Publication type: Article

Publication status: Published

Journal: Ophthalmology

Year: 2010

Volume: 117

Issue: 8

Pages: 1538-1546

Print publication date: 01/08/2010

ISSN (print): 0161-6420

ISSN (electronic): 1549-4713

Publisher: Elsevier


DOI: 10.1016/j.ophtha.2009.12.038


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Funder referenceFunder name
Academy of Medical Sciences
UK National Commissioning Group
Wellcome Trust
Medical Research Council Translational Muscle Centre
Newcastle upon Tyne Hospitals NHS Charity
Parkinson's Disease Society (UK)
UK NIHR Biomedical Research Centre in Ageing and Age-related Disease
HO 2505/2-1Deutsche Forschungsgemeinschaft