Pathogenic mitochondrial DNA mutations and associated clinical features in Korean patients with Leber's hereditary optic neuropathy

Purpose: To identify the spectrum of pathogenic mitochondrial DNA (mtDNA) mutations and clinical features in Korean patients with genetically confirmed Leber's hereditary optic neuropathy (LHON).

Methods: The medical records of 34 unrelated, genetically confirmed LHON patients were reviewed. Total genomic DNA was isolated from the peripheral blood leukocytes of the patients with suspected LHON, and primary or secondary mtDNA mutations were identified by direct sequencing. We analyzed the visual acuity (VA), color vision, RNFL thickness, and visual field (VF) at the final visit from 20 patients who were followed-up for more than 6 months after the onset of LHON.

Results: Among 34 patients, 21 (61.8%) had the homoplasmic primary mutation, 11 (32.4%) had the homoplasmic secondary mutation, and 2 (5.9%) had the heteroplasmic primary mutation along with the homoplasmic secondary mutation. Analysis of mtDNA sequences revealed six different types of LHON-associated mutations: two primary LHON-associated primary mutations, m.11778G>A (20 patients, 58.8%) and m.14484T>C (3 patients, 8.8%), and four secondary LHON-associated mutations, which were m.3394T>C (3 patients, 8.8%), m.3497C>T (4 patients, 11.8%), m.11696G>A (4 patients, 11.8%), and m.14502T>C (2 patients, 5.9%). Secondary mutation-carrying patients demonstrated a decreased in RNFL thickness, similar to those in primary mutation-carrying LHON patients. These patients had a higher female ratio (P = 0.019), better VA (P = 0.043) and color vision (P = 0.005), as well as better VF.

Conclusions: In addition to common primary LHON-associated mutations, our study identified secondary mtDNA mutations, which should be considered when evaluating patients with optic atrophy.