Abstract
SCO2 mutations cause recessively inherited cytochrome c oxidase deficiency. Recently Tran-Viet et al. proposed that heterozygosity for pathogenic SCO2 variants, including the common E140K variant, causes high-grade myopia. To investigate the association of SCO2 mutations with myopia, ophthalmic examinations were performed on 35 E140K carriers, one homozygous infant, and on a mouse model of Sco2 deficiency. Additionally, a screen for other putative effects of SCO2 heterozygosity was carried out by comparing the prevalence of the common E140K variant in a population of patients with undiagnosed diseases compatible with SCO2-related pathogenesis to that in a general population sample. High-grade myopia was not identified in any of the studied individuals. Of the carriers, 17 were emmetropic, and 18 possessed refractive errors. Additionally, no significant axial elongation indicative of high-grade myopia was found in mice carrying E129K (corresponding to E140K in humans) knock-in mutations. The prevalence of E140K carriers in the symptomatic cohort was evaluated as 1:103 (CI: 0.44–2.09) and did not differ significantly from the population prevalence (1:147, CI: 0.45–1.04).
Our study demonstrates that heterozygosity for pathogenic SCO2 variants is not associated with high-grade myopia in either human patients or in mice.
Competing interests: None declared
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Acknowledgements
We are grateful to parents of affected infants participating in the survey.
The study was supported by grants from the National Science Centre 1154/B/P01/2011/40, 2012/05/B/NZ2/01627 and the CMHI projects S211/10, S136/13, and S126/12; grants from the US National Institutes of Health (EY013435, EY019007, EY023595, HD032062, and HD080642) and the US Department of Defense (W911NF-12-1-9159 and W911F-15-1-0169); and an unrestricted grant to the Department of Ophthalmology of Columbia University from Research to Prevent Blindness, the Muscular Dystrophy Association, and the J. Willard and Alice S. Marriott Foundation. This publication was also supported by Career Development Awards from Research to Prevent Blindness, the Louis V. Gerstner Jr. Scholars Program, and the AR and JR Peacock Trust.
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Communicated by: Verena Peters
Appendices
Take-Home Message
The heterozygosity for pathogenic SCO2 variants is not associated with high-grade myopia in either human patients or in mice.
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The authors of this manuscript declare that there are no conflicts of interest.
Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
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All institutional and national guidelines for the care and use of laboratory animals were followed.
Details of the Contributions of Individual Authors
DPA devised study protocol, analyzed the data, conceived the purpose of the manuscript, and wrote the article.
BKK performed ophthalmological assessments analysis and assisted in writing the manuscript.
SŁ and MM performed population studies and analyzed the data.
OS, KC, and PK performed population studies.
KIP, JP, JZ, JZ, MKW, and EC collected previous data and assisted in reviewing and editing the manuscript.
RP conducted whole genome sequencing experiments and assisted in writing the manuscript.
EAS designed experiments, analyzed the data, and assisted in writing the paper.
SS designed experiments, assisted with experiments, and analyzed the data.
HY designed experiments and assisted with experiments.
QW assisted with experiments and analyzed the data.
QH designed experiments, assisted with experiments, analyzed the data, and assisted in writing the manuscript.
RS assisted with experiments.
EP conceived the purpose of the manuscript, analyzed the data, and involved in writing and editing the manuscript.
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Piekutowska-Abramczuk, D. et al. (2015). No Evidence for Association of SCO2 Heterozygosity with High-Grade Myopia or Other Diseases with Possible Mitochondrial Dysfunction. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 27. JIMD Reports, vol 27. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_468
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DOI: https://doi.org/10.1007/8904_2015_468
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