The novel mitochondrial tRNA Asn gene mutation m.5709T>C produces ophthalmoparesis and respiratory impairment

摘要

Although mutations in mitochondrial tRNAs constitute the most common mtDNA defect, the presence of pathological variants in mitochondrial tRNA Asn is extremely rare. We were able to identify a novel mtDNA tRNA Asn gene pathogenic mutation associated with a myopathic phenotype and a previously unreported respiratory impairment. Our proband is an adult woman with ophthalmoparesis and respiratory impairment. Her muscle biopsy presented several cytochrome c oxidase-negative (COX) fibres and signs of mitochondrial proliferation (ragged red fibres). Sequence analysis of the muscle-derived mtDNA revealed an m.5709TC substitution, affecting mitochondrial tRNA Asn gene. Restriction-fragment length polymorphism analysis of the mutation in isolated muscle fibres showed that a threshold of at least 91.9% mutated mtDNA results in the COX deficiency phenotype. The new phenotype further increases the clinical spectrum of mitochondrial diseases caused by mutations in the tRNA Asn gene.