Mutation m.15923A>G in the MT-TT gene causes mild myopathy - case report of an adult-onset phenotype

• Published in: BMC neurology Vol. 18; no. 1; p. 149
• Main Authors: Kärppä, Mikko, Kytövuori, Laura, Saari, Markku, Majamaa, Kari
• Format: Journal Article
• Language: English
• Published: England BioMed Central 20.09.2018; BMC
• Subjects: Adult; Age; Age of Onset; Biopsy; Case Report; Case reports; Children; Cytochrome; Cytochrome c; Deoxyribonucleic acid; Disease; DNA; DNA, Mitochondrial - genetics; Epilepsy; Epithelial cells; Genes; Heteroplasmy; Histology; Humans; Intolerance; Male; MERRF Syndrome; Mitochondria; Mitochondrial diseases; Mitochondrial DNA; Mitochondrial tRNAThr; Muscle, Skeletal - pathology; Muscular Diseases - genetics; Muscular Diseases - pathology; Mutation; Myopathy; Neuromuscular disorders; Patients; Phenotype; Phenotypes; RNA, Transfer - genetics; Single-fibre analysis; Skeletal muscle; Threonine; Threonine - genetics; tRNA; Finland; Case report; Mitochondrial diseases; Neuromuscular disorders; Single-fibre analysis; Mitochondrial tRNAThr
• ISSN: 1471-2377; 1471-2377
• DOI: 10.1186/s12883-018-1159-4

Only five patients have previously been reported to harbor mutations in the MT-TT gene encoding mitochondrial tRNA threonine. The m.15923A > G mutation has been found in three severely affected children. One of these patients died within days after birth and two had a phenotype of myoclonic epilepsy with ragged red fibers (MERRF) in early childhood. We have now found the mutation in an adult patient with mild myopathy. The patient is a 64-year-old Finnish man, who developed bilateral ptosis, diplopia and exercise intolerance in his fifties. Family history was unremarkable. Muscle histology showed cytochrome c-oxidase (COX) negative and ragged red fibres. The m.15923A > G mutation heteroplasmy was 33% in the skeletal muscle and 2% in buccal epithelial cells. The mutation was undetectable in the blood. Single-fibre analysis was performed and COX-negative fibres had a substantially higher heteroplasmy of 92%, than the normal fibres in which it was 43%. We report the fourth patient with m. 15923A > G and with a remarkably milder phenotype than the previous three patients. Our findings and recent biochemical studies suggest that the mutation m.15923A > G is a definite disease-causing mutation. Our results also suggest that heteroplasmy of the m.15923A > G mutation correlates with the severity of the phenotype. This study expands the catalog of the phenotypes caused by mutations in mtDNA.