Is the disease risk and penetrance in Leber hereditary optic neuropathy actually low?
LHON
UK Biobank
haplogroup
m.11778G>A
m.14484T>C
mitochondria
mtDNA
myocilin
prevalence
Journal
American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475
Informations de publication
Date de publication:
05 01 2023
05 01 2023
Historique:
received:
08
10
2022
accepted:
21
11
2022
pubmed:
25
12
2022
medline:
11
1
2023
entrez:
24
12
2022
Statut:
ppublish
Résumé
Pedigree 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.
Identifiants
pubmed: 36565701
pii: S0002-9297(22)00505-5
doi: 10.1016/j.ajhg.2022.11.014
pmc: PMC9892764
pii:
doi:
Substances chimiques
DNA, Mitochondrial
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
170-176Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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