Clinical phenotype and the G11778A mutation of mitochondrial DNA in patients with Leber’s hereditary optic neuropathy in Taiwan

Abstract

We report the clinical manifestations and mitochondrial DNA (mtDNA) mutations of nine Chinese patients with Leber's hereditary optic neuropathy from seven families in Taiwan. The nine probands were all males, aged 19 to 43 years at the time of the study and with ages of onset ranging between 13 and 30 years. They were characterized by an acute or subacute onset of visual loss in one eye, which progressed to the other eye within a few weeks. Their visual outcome was poor, although improvement was noted in four patients. A muscle biopsy from one patient showed a decreased activity of cytochrome c oxidase and subsarcolemmal mitochondrial aggregation. All patients and unaffected maternal family members had a homoplasmic G11778A mtDNA mutation regardless of variations in clinical manifestation. High frequencies of environmental factors such as smoking, alcohol consumption, trauma, and/or military training were found in these patients. We conclude that even though a homoplasmic G11778A mtDNA mutation was found in all patients and their maternal family members, this mutation could not account for the presentation of the clinical features. Additional genetic, epigenetic, and/or environmental factors may be important trigger factors in the clinical expression. LHON in Taiwan 207 Original paperNeuroophthalmology Downloaded from informahealthcare.com by The University of Manchester on 11/03/14For personal use only.Neuroophthalmology Downloaded from informahealthcare.com by The University of Manchester on 11/03/14For personal use only.

Current and Future Landscape in Genetic Therapies for Leber Hereditary Optic Neuropathy

“…By ubiquinone, electrons are shuttled from complexes I and II to complex III during the mitochondrial respiratory chain. A significant improvement in visual acuity was reported after 4 months of oral treatment with increasing coenzyme Q10 [71]. Treatment with combination therapies of CoQ10 and other nutritional supplements improved plasma lactate concentrations, body composition, ankle dorsiflexion strength, and oxidative stress in patients with LHON [72].…”

Varying Clinical Phenotypes of Mitochondrial DNA T12811C Mutation: A Case Series Report

“…Although visual dysfunction is the most common symptom of LHON, other systemic abnormalities can also occur. These include dystonia, Parkinsonism, extra-pyramidal motor symptoms, peripheral neuropathy, cardiac conduction abnormalities, spinal cord disease, and skeletal muscle abnormalities (6)(7)(8)(9)(10)(11)(12)(13). The maternal transmission indicates that mutations in the mitochondrial DNA (mtDNA) play key roles in the development of LHON.…”