Lightning strikes twice: Leber hereditary optic neuropathy families with two pathogenic mtDNA mutations

Neil Howell, Neil R. Miller, David A. Mackey, Anthony Arnold, Corinna Herrnstadt, Isla M. Williams, Iwona Kubacka

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Objective: To report the clinical and mitochondrial genetic analyses of two families, each of which carries both the 11778 and 14484 Leber hereditary optic neuropathy (LHON) mutations in mitochondrial DNA. Methods: In addition to detailed clinical histories, the complete sequence of the mitochondrial DNA (mtDNA) from each family was determined. Results: A small Australian LHON family (Vic20) and a family from the United States carry the 11778 and 14484 LHON mutations. In addition to the optic neuropathy, one branch of the Baltimore LHON pedigree had a high incidence of a fatal infantile encephalopathy. In both families, the 14484 LHON mutation was homoplasmic, whereas the 11778 LHON mutation was heteroplasmic. Conclusions: There are no additional mtDNA sequence changes that explain the encephalopathy in the Baltimore LHON family, and a nuclear gene involvement is an alternative explanation that is supported by the available data. The ophthalmological characteristics and penetrance in the 11778 and 14484 "two-mutation" LHON families are not markedly more severe than those of classic LHON families who carry a single mtDNA mutation.

Original languageEnglish
Pages (from-to)262-269
Number of pages8
JournalJournal of Neuro-Ophthalmology
Volume22
Issue number4
DOIs
Publication statusPublished - 1 Jan 2002
Externally publishedYes

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