This report describes progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2; the human gene implicated in this disease is SLC25A4, which encodes a mitochondrial ADP/ATP translocator. SLC25A4 is implicated in more than one mitochondrial disease (MIM:103220). For information on experimental results using Drosophila models of this and related diseases see the human disease model report 'mitochondrial disease and seizure sensitivity, SLC25A4(ANT1)-related' (FBhh0000372).
[updated Aug. 2016 by FlyBase; FBrf0222196]
Progressive external ophthalmoplegia is characterized by multiple mitochondrial DNA deletions in skeletal muscle. The most common clinical features include adult onset of weakness of the external eye muscles and exercise intolerance. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. Both autosomal dominant and autosomal recessive inheritance can occur; autosomal recessive inheritance is usually more severe (Filosto et al., 2003, pubmed:12975295; Luoma et al., 2004, pubmed:15351195) [from MIM:157640; 2019.02.19]
[PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT 2; PEOA2](https://omim.org/entry/609283)
[SOLUTE CARRIER FAMILY 25 (MITOCHONDRIAL CARRIER, ADENINE NUCLEOTIDE TRANSLOCATOR), MEMBER 4; SLC25A4](https://omim.org/entry/103220)
Progressive external ophthalmoplegia is a condition characterized by weakness of the eye muscles. There may also be general weakness of the muscles used for movement (myopathy), particularly those in the neck, arms, or legs, which may be especially noticeable during exercise (exercise intolerance). Muscle weakness may also cause difficulty swallowing (dysphagia). [from Genetics Home Reference, progressive external ophthalmoplegia; 2016.08.25]
The most common clinical features of PEOA2 include adult onset of weakness of the external eye muscles and exercise intolerance. [from MIM:609283; 2016.08.25]
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2 (PEOA2) is caused by caused by heterozygous mutation in the nuclear-encoded gene SLC25A4 (ANT1). [from MIM:609283; 2016.08.25]
The SLC25A4 gene encodes a mitochondrial ADP/ATP translocator (also known as adenine nucleotide translocator 1, ANT1), which is a homodimer of 30-kD subunits embedded in the mitochondrial inner membrane. The dimer forms a gated pore through which ADP is moved across the inner membrane into the mitochondrial matrix and ATP is moved from the matrix into the cytoplasm (summary by Neckelmann et al., 1987; pubmed:2823266). [from MIM:103220; 2016.08.25]
