2020/09/01 by Kittichate Visuttijai, Carola Hedberg‐Oldfors, Ulrika Lindgren +4
Biochemistry, Genetics and Molecular Biology · #Connective tissue disorders research #Mitochondrial Function and Pathology #Muscle Physiology and Disorders
paper · pdf · doi:10.1111/ane.13339
openalex publication_date 2020/09/01 · crossref created 2020/09/01 · openalex created_date 2020/09/08 · crossref issued 2020/09/19 · crossref published 2020/09/19 · crossref published-online 2020/09/19 · crossref published-print 2021/01/01 · crossref deposited 2022/12/20 · openalex updated_date 2026/08/04 · crossref indexed 2026/08/04
Objectives To describe two patients with progressive external ophthalmoplegia (PEO) and mitochondrial myopathy associated with mutations in mitochondrial DNA, encoding the tRNAAsn gene (MT-TN), which have not previously been published with clinical descriptions. Materials & Methods Two unrelated patients with PEO were clinically examined. Muscle biopsy was performed and investigated by exome sequencing, enzyme histochemistry, and immunohistochemistry. The level of heteroplasmy was investigated in single muscle fibers and in other tissues. Results Patient 1 was a 52-year-old man with ptosis, PEO, and exercise intolerance since childhood. Muscle biopsy demonstrated mitochondrial myopathy with frequent cytochrome c oxidase (COX)-deficient fibers and a heteroplasmic mutation, m.5669G>A in the MT-TN gene, resulting in a substitution of a highly conserved C to T in the T stem of tRNAAsn. Patient 2 was a 66-year-old woman with ptosis, PEO, and exercise intolerance since many years. Muscle biopsy demonstrated mitochondrial myopathy with frequent COX-deficient fibers. She had a novel m.5702delA mutation in MT-TN, resulting in loss of a highly conserved U in the anticodon stem of tRNAAsn. Single fiber analysis in both cases showed highly significant differences in mutation load between COX-deficient and COX-normal fibers and a high threshold level for COX deficiency. The mutations were not found in blood, urine sediment or buccal cells. Conclusion We describe two MT-TN mutations associated with PEO and mitochondrial myopathy, and their pathogenicity was demonstrated. Together with previous reports, the results indicate that MT-TN is a hot spot for mutations causing sporadic PEO.