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Catarino, C.B.* ; Ahting, U.* ; Gusic, M. ; Iuso, A. ; Repp, B. ; Peters, K.* ; Biskup, S.* ; von Livonius, B.* ; Prokisch, H. ; Klopstock, T.*

Characterization of a Leber's hereditary optic neuropathy (LHON) family harboring two primary LHON mutations m.11778G>A and m.14484T>C of the mitochondrial DNA.

Mitochondrion 36, 15-20 (2016)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Leber's hereditary optic neuropathy (LHON) is an inherited mitochondrial disease that usually leads to acute or subacute bilateral central vision loss. In 95% of cases, LHON is caused by one of three primary mutations of the mitochondrial DNA (mtDNA), m.11778G>A in the MT-ND4 gene, m.14484T>C in the MT-ND6 gene, or m.3460G>A in the MT-ND1 gene. Here we characterize clinically, genetically, and biochemically a LHON family with multiple patients harboring two of these primary LHON mutations, m.11778G>A homoplasmic and m.14484T>C heteroplasmic. The unusually low male-to-female ratio of affected family members is also seen among the other patients previously reported with two primary LHON mutations m.11778G>A and m.14484T>C. While the index patient had very late onset of symptoms at 75years and severe visual loss, her two daughters had both onset in childhood (6 and 9years), with moderate to mild visual loss. A higher degree of heteroplasmy of the m.14484T>C mutation was found to correlate with an earlier age at onset in this family. Ours is the first LHON family harboring two primary LHON mutations where functional studies were performed in several affected family members. A more pronounced bioenergetic defect was found to correlate with an earlier age at onset. The patient with the earliest age at onset had a more significant complex I dysfunction than all controls, including the LHON patient with only the m.11778G>A mutation, suggesting a synergistic effect of the two primary LHON mutations in this patient.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Complex I ; Lhon ; Mitochondrial Dna ; Mitochondriopathy ; Oxidative Phosphorylation ; Respiratory Chain
ISSN (print) / ISBN 1567-7249
e-ISSN 1872-8278
Journal Mitochondrion
Quellenangaben Volume: 36, Issue: , Pages: 15-20 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Oxford
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)