OMIM ID:
External Ophthalmoplegia, ANT1 and mtDNA Mutations
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Ptosis and progressive external ophthalmoplegia are the outstanding features of this form of external ophthalmoplegia. These symptoms may appear in early adulthood. A few patients have had thyroid disease as well. Muscle biopsies from limb muscles show the characteristic ragged red appearance of myopathy in a minority of fibers. Multiple deletions occur in the mitochondria of skeletal muscles. EMG studies show myopathy while nerve conduction studies are normal. Respiratory chain analysis often shows evidence of mitochondrial dysfunction.
Genetics
Inheritance
This autosomal dominant disorder results from the combination of a mutation in the ANT1 (SLC25A4) gene (4q35) (encoding the adenine nucleotide translocator-1) and mitochondrial DNA deletions. About 11% of autosomal dominant cases with progressive external ophthalmoplegia have mutations in this gene. Most reported families have been from Italy.
External ophthalmoplegia may also result from mutations in POLG (most common), and in C10ORF2.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission