A novel mitochondrial ND5 gene mutation m.13042G>A in Leber hereditary optic neuropathy

Abstract

Purpose To report clinical and genetic characterization of two related patients with Leber hereditary optic neuropathy (LHON). Methods A 20‐year old man was referred in September 2004 for acute, painless and severe visual loss in his left eye, and then three weeks later in the other. Visual acuity (VA) on presentation was 0.2 in his right eye and HM in his left eye. His 11‐year old cousin was referred in December 2006 for acute and painless visual loss on both eyes with VA of CF in his right eye and 0,3 on his left eye. Fundus examination in both patients revealed engorged optic disc with telangectatic and tortuous vessels with no leakage on fluorescein angiography. MRI of brain was normal in both patients. There were loss of N95 vawe in PERG and abnormal VEP suggesting retinal ganglion cell loss and optic nerve disease. In first patient, VA decreased to HM on both eyes in few months and in 4,5 year follow up didn’t improve.In second patient, VA decreased to 0.001 on right eye and 0.04 on left eye in 2,5 year follow up. Results Genetic tests of the mitochondrial(MT) DNA for three most common mutations (m.11778 G> A, m.3460 G>A, m.14484 T>C) responsible for LHON were negative in both patients. Use of Mito‐Chip 2 didn't reveal any mutations,whilst sequencing the entire MT‐genome in the first patient revealed mutation m.13042G>A (homoplasmy) in gene MT‐ND5; for second patient sequencing for this mutation is in process. Conclusion This mutation has not been previously described in association with LHON and was not mentioned in mtDB or mtSNP (single nucleotide polymorphism) database (DB). The mutation is likely to be causative of the disease since no other mutations were found in MT‐genome in a patient with typical clinical presentation of LHON.