Abstract • Objective. —To define the clinical features of Leber's hereditary optic neuropathy associated with the 14484 mitochondrial DNA mutation and to compare these features with those associated with three other pathogenetic mutations. Design and Patients. —Clinical and historical data were collected from 19 visually symptomatic patients from 17 independent pedigrees with the molecularly confirmed 14484 mutation. Main Outcome Measures. —Demographic features, age of onset of visual loss, nadir of visual acuity, occurrence and timing of visual recovery, family history of visual loss, and associated medical and environmental conditions. Results. —Clinical characteristics associated with the 14484 mutation are similar overall to those of the three other primary mutations. One notable distinguishing feature is the higher incidence of visual recovery among patients with the 14484 mutation. Thirty-seven percent of our patients experienced visual recovery compared with 5% with the 11778 mutation (P<.001), 22% with the 3460 mutation, and 29% with the 15257 mutation. The average age of onset of visual symptoms for the patients with the 14484 mutation who had visual recovery was younger than for those without recovery (19.6 vs 30.6 years). Thirteen of the 19 patients had a history of metabolic disturbance, trauma, or substance abuse. Conclusions. —Leber's hereditary optic neuropathy associated with the 14484 mitochondrial DNA mutation may have a better prognosis for visual recovery. The phenotypic expression of the 14484 mutation may be influenced by concurrent medical and environmental factors. Molecular genetic testing in suspected Leber's hereditary optic neuropathy is useful to confirm the diagnosis and to assess visual prognosis. References 1. Wallace DC, Singh G, Lott MT, et al. Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy . Science . 1988;242:1427-1430.Crossref 2. Huoponen K, Vilkki J, Aula P, Nikoskelainen EK, Savontaus ML. A new mtDNA mutation associated with Leber's hereditary optic neuropathy . Am J Hum Genet . 1991;48:1147-1153. 3. Howell N, Bindoff LA, McCullough DA, et al. Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees . Am J Hum Genet . 1991;49:939-950. 4. Johns DR, Neufeld MJ. Cytochrome b mutations in Leber hereditary optic neuropathy . Biochem Biophys Res Commun . 1991;181:1358-1364.Crossref 5. Brown MD, Voljavec AS, Lott MT, Torroni A, Yang CC, Wallace DC. Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy . Genetics . 1992;130:163-173. 6. Johns DR, Neufeld MJ, Park RD. An ND-6 mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy . Biochem Biophys Res Commun . 1992;187:1551-1557.Crossref 7. Howell N, Kubacka I, Xu M, McCullough DA. Leber hereditary optic neuropathy: involvement of the ND1 gene and evidence for an intragenic suppressor mutation . Am J Hum Genet . 1991;48:935-942. 8. Johns DR, Berman J. Alternative simultaneous complex I mitochondrial DNA mutations in Leber's hereditary optic neuropathy . Biochem Biophys Res Commun . 1991;174:1324-1330.Crossref 9. Newman NJ, Lott MT, Wallace DC. The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation . Am J Ophthalmol . 1991;111:750-762. 10. Johns DR, Smith KH, Miller NR. Leber's hereditary optic neuropathy: clinical manifestations of the 3460 mutation . Arch Ophthalmol . 1992;110:1577-1581.Crossref 11. Johns DR, Smith KH, Savino PJ, Miller NR. Leber's hereditary optic neuropathy: clinical manifestations of the 15257 mutation. Ophthalmology. In press. 12. Morse RM, Flavin DK. The definition of alcoholism . JAMA . 1992;268:1012-1014.Crossref 13. Stone EM, Newman NJ, Miller NR, Johns DR, Lott MT, Wallace DC. Visual recovery in patients with Leber's hereditary optic neuropathy and the 11778 mutation . J Clin Neuro Ophthalmol . 1992;12:10-14.
Archives of Ophthalmology – American Medical Association
Published: Apr 1, 1993