Identification of a Novel mtDNA Mutation in a Family with an Anterior Ischemic Optic Neuropathy Phenotype

Abstract

Abstract: : Purpose: Six members of a pedigree were each diagnosed with anterior ischemic optic neuropathy (AION) in their 40’s or 50’s. These patients were screened for mitochondrial mutations to determine if they were actually affected with a late-onset form of Leber’s hereditary optic neuropathy (LHON) rather than true AION. Methods: The mitochondrial DNA of the proband was sequenced and then compared against the revised Cambridge reference sequence. When a novel mutation that changed an amino acid was identified in the ND1 gene of the proband, other family members, 41 AION patients, and 1488 LHON probands were screened for this mutation. Results: Six affected members of this family first developed symptoms of AION in their forties or fifties, and all were related to one another through females. A novel mitochondrial mutation was identified in all six family members who had been diagnosed with AION. A guanine to adenine change was identified at position 4132 which would be expected to cause an ALA276THR change in the protein encoded by the ND1 gene. Four unaffected family members also harbored this mutation, but it was not identified in any of the 41 AION or the 1488 typical LHON probands in the study. Conclusions: A novel mitochondrial DNA mutation (4132 G->A) is associated with late onset Leber’s hereditary optic neuropathy. This mutation appears to be rare since it was not identified in a large group of LHON patients.

Keywords: genetics • mutations • molecular biology