Establishing risk of vision loss in Leber hereditary optic neuropathy

M. Isabel G. Lopez Sanchez, Lisa S. Kearns, Sandra E. Staffieri, Linda Clarke, Myra B. McGuinness, Wafaa Meteoukki, Sona Samuel, Jonathan B. Ruddle, Celia Chen, Clare L. Fraser, John Harrison, Alex W. Hewitt, Neil Howell, David A. Mackey*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)
28 Downloads (Pure)

Abstract

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 We identified 96 genetically unrelated LHON pedigrees, including 56 unpublished pedigrees, and updated 40 previously known pedigrees, comprising 620 affected individuals and 4,948 asymptomatic carriers.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.

Original languageEnglish
Pages (from-to)2159-2170
Number of pages12
JournalAmerican Journal of Human Genetics
Volume108
Issue number11
DOIs
Publication statusPublished - 4 Nov 2021
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • blindness
  • epidemiology
  • genetic counseling
  • LHON
  • mitochondria
  • optic atrophy
  • penetrance
  • risk
  • vision loss

Fingerprint

Dive into the research topics of 'Establishing risk of vision loss in Leber hereditary optic neuropathy'. Together they form a unique fingerprint.

Cite this