Low disease risk and penetrance in Leber hereditary optic neuropathy.
Am J Hum Genet
; 110(1): 166-169, 2023 01 05.
Article
en En
| MEDLINE
| ID: mdl-36565700
ABSTRACT
The risk of Leber hereditary optic neuropathy (LHON) has largely been extrapolated from disease cohorts, which underestimate the population prevalence of pathogenic primary LHON variants as a result of incomplete disease penetrance. Understanding the true population prevalence of primary LHON variants, alongside the rate of clinical disease, provides a better understanding of disease risk and variant penetrance. We identified pathogenic primary LHON variants in whole-genome sequencing data of a well-characterized population-based control cohort and found that the prevalence is far greater than previously estimated, as it occurs in approximately 1 in 800 individuals. Accordingly, we were able to more accurately estimate population risk and disease penetrance in LHON variant carriers, validating our findings by using other large control datasets. These findings will inform accurate counseling in relation to the risk of vision loss in LHON variant carriers and disease manifestation in their family. This Matters Arising paper is in response to Lopez Sanchez et al. (2021), published in The American Journal of Human Genetics. See also the response by Mackey et al. (2022), published in this issue.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Atrofia Óptica Hereditaria de Leber
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Año:
2023
Tipo del documento:
Article