A novel D104G mutation in the adenine nucleotide translocator 1 gene in autosomal dominant progressive external ophthalmoplegia patients with mitochondrial DNA with multiple deletions.
Autosomal dominant progressive external ophthalmoplegia is a mitochondrial disorder characterized by multiple large deletions of mitochondrial DNA. A recent study showed pathogenic heterozygous missense mutations in the heart/skeletal muscle isoform of the adenine nucleotide translocator 1 gene in autosomal dominant progressive external ophthalmoplegia patients. In one Japanese autosomal dominant progressive external ophthalmoplegia family, we found a novel A-to-G heterozygous mutation at nucleotide 311 of the adenine nucleotide translocator 1 gene, which segregated with affected individuals and could not be detected in the genomic DNA sequence of 120 normal controls. This mutation converted a highly conserved aspartic acid into a glycine at codon 104. Polymerase chain reaction analysis of single muscle fibers showed the presence of one type of deletion in each fiber, suggesting clonal expansion of mitochondrial DNA with deletions. These findings support the pathogenesis of the adenine nucleotide translocator 1 gene mutation in human disease.
Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Hirofumi
H
Komaki
Toshiyuki
T
Fukazawa
Hideki
H
Houzen
Kazuto
K
Yoshida
Ikuya
I
Nonaka
Yu-ichi
Y
Goto
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005799:Genes, Dominant; D005998:Glycine / Q000235:genetics*; D006801:Humans; D000226:Mitochondrial ADP, ATP Translocases / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics*; D010375:Pedigree
D004272:DNA, Mitochondrial; D001224:Aspartic Acid; D000226:Mitochondrial ADP, ATP Translocases; D005998:Glycine