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Low penetrance of the 14484 LHON mutation when it arises in a non-haplogroup J mtDNA background

Version 2 2024-09-17, 02:06
Version 1 2023-05-16, 20:35
journal contribution
posted on 2024-09-17, 02:06 authored by N Howell, C Herrnstadt, David MackeyDavid Mackey
The penetrance in Leber's hereditary optic neuropathy (LHON) pedigrees is determined primarily by a mutation in the mitochondrial genome (mtDNA), but secondary factors are also necessary for manifestation of the disorder. It has been proposed that mtDNA polymorphisms affect penetrance in LHON pedigrees. In particular, it has been postulated that one or more polymorphisms associated with European haplogroup J mtDNAs substantially increase the penetrance of the primary LHON mutation at nucleotide 14484. We report here a haplogroup H matrilineal pedigree (VIC14) in which the single affected member carries the 14484 LHON mutation, but who manifested a milder and atypical optic nerve disorder. In addition, during a population screen, we identified an individual who carried the 14484 mutation but who had normal vision. Finally, the 14484 mutation is under-represented among haplogroup H mtDNAs that carry a LHON mutation. These results, in conjunction with other studies that are reviewed, indicate that 14484 LHON mutations have a low penetrance when they arise in a haplogroup H mtDNA background.

History

Publication title

American Journal of Medical Genetics. Part A

Volume

119A

Issue

2

Pagination

147-151

ISSN

0148-7299

Department/School

Menzies Institute for Medical Research

Publisher

John Wiley & Sons, Inc.

Publication status

  • Published

Place of publication

United States

Socio-economic Objectives

200199 Clinical health not elsewhere classified

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