155573 - Is the disease risk and penetrance in Leber hereditary optic neuropathy actually low_.pdf (1016.01 kB)
Is the disease risk and penetrance in Leber hereditary optic neuropathy actually low?
journal contribution
posted on 2023-05-21, 16:44 authored by David MackeyDavid Mackey, Ong, JS, MacGregor, S, Whiteman, DC, Craig, JE, Lopez Sanchez, MIG, Kearns, LS, Staffieri, SE, Clarke, L, McGuinness, MB, Meteoukki, W, Samuel, S, Ruddle, JB, Chen, C, Fraser, CL, Harrison, J, Howell, N, Alexander HewittAlexander HewittPedigree analysis showed that a large proportion of Leber hereditary optic neuropathy (LHON) family members who carry a mitochondrial risk variant never lose vision. Mitochondrial haplotype appears to be a major factor influencing the risk of vision loss from LHON. Mitochondrial variants, including m.14484T>C and m.11778G>A, have been added to gene arrays, and thus many patients and research participants are tested for LHON mutations. Analysis of the UK Biobank and Australian cohort studies found more than 1 in 1,000 people in the general population carry either the m.14484T>C or the m.11778G>A LHON variant. None of the subset of carriers examined had visual acuity at 20/200 or worse, suggesting a very low penetrance of LHON. Haplogroup analysis of m.14484T>C carriers showed a high rate of haplogroup U subclades, previously shown to have low penetrance in pedigrees. Penetrance calculations of the general population are lower than pedigree calculations, most likely because of modifier genetic factors. This Matters Arising Response paper addresses the Watson et al. (2022) Matters Arising paper, published concurrently in The American Journal of Human Genetics.
History
Publication title
American Journal of Human GeneticsVolume
110Pagination
170-176ISSN
0002-9297Department/School
Menzies Institute for Medical ResearchPublisher
Cell PressPlace of publication
United StatesRights statement
Copyright 2022 The Author(s). This is an open access article under the Creative Commons Attribution 4.0 International (CC BY 4.0) license (http://creativecommons.org/licenses/by/4.0/).Repository Status
- Open