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Establishing risk of vision loss in Leber hereditary optic neuropathy


Lopez Sanchez, MIG and Kearns, LS and Staffieri, SE and Clarke, L and McGuinness, MB and Meteoukki, W and Samuel, S and Ruddle, JB and Chen, C and Fraser, CL and Harrison, J and Hewitt, AW and Howell, N and Mackey, DA, Establishing risk of vision loss in Leber hereditary optic neuropathy, American Journal of Human Genetics, 108, (11) pp. 2159-2170. ISSN 0002-9297 (2021) [Refereed Article]


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Copyright 2021 The Author(s). This is an open access article under the CC BY license (

DOI: doi:10.1016/j.ajhg.2021.09.015


We conducted an updated epidemiological study of Leber hereditary optic neuropathy (LHON) in Australia by using registry data to establish the risk of vision loss among different LHON mutations, sex, age at onset, and mitochondrial haplogroup. We identified 96 genetically unrelated LHON pedigrees, including 56 unpublished pedigrees, and updated 40 previously known pedigrees, comprising 620 affected individuals and 4,948 asymptomatic carriers. The minimum prevalence of vision loss due to LHON in Australia in 2020 was one in 68,403 individuals. Although our data confirm some well-established features of LHON, the overall risk of vision loss among those with a LHON mutation was lower than reported previously-17.5% for males and 5.4% for females. Our findings confirm that women, older adults, and younger children are also at risk. Furthermore, we observed a higher incidence of vision loss in children of affected mothers as well as in children of unaffected women with at least one affected brother. Finally, we confirmed our previous report showing a generational fall in prevalence of vision loss among Australian men. Higher reported rates of vision loss in males with a LHON mutation are not supported by our work and other epidemiologic studies. Accurate knowledge of risk is essential for genetic counseling of individuals with LHON mutations. This knowledge could also inform the detection and validation of potential biomarkers and has implications for clinical trials of treatments aimed at preventing vision loss in LHON because an overestimated risk may lead to an underpowered study or a false claim of efficacy.

Item Details

Item Type:Refereed Article
Keywords:LHON, blindness, epidemiology, genetic counseling, mitochondria, optic atrophy, penetrance, risk, vision loss
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Treatment of human diseases and conditions
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
UTAS Author:Mackey, DA (Professor David Mackey)
ID Code:151709
Year Published:2021
Web of Science® Times Cited:9
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-08-03
Last Modified:2022-09-08
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