Mitochondrial myopathy and ophthalmoplegia in a sporadic patient with the G12315A mutation in mitochondrial DNA

Abstract A 21-year-old woman described proximal muscle weakness since early childhood. At age 16, she developed bilateral ptosis, progressive external ophthalmoplegia, and exercise intolerance. She harbored a heteroplasmic G12315A mutation in the mitochondrial DNA tRNA Leu(CUN) gene, which disrupts a highly conserved G-C base pair in the TΨC stem of the molecule. Mutant mitochondrial DNA was 62% of total in muscle and 17% in blood. The mutation was undetectable in blood, urinary sediment, and hair follicles from the patient's mother. This second patient with G12315A and progressive external ophthalmoplegia confirms the pathogenicity of the mutation and helps to define the correlation between genotype and phenotype.