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Publication . Article . 2019

A novel mitochondrial m.4414T > C MT-TM gene variant causing progressive external ophthalmoplegia and myopathy

Hellebrekers, Debby M.E.I.; Blakely, Emma L.; Hendrickx, Alexandra T.M.; Hardy, Steven A.; Hopton, Sila; Falkous, Gavin; de Coo, Irenaeus F.M.; +3 Authors
Open Access   English  
Published: 01 Sep 2019 Journal: Neuromuscular Disorders, volume 29, issue 9, pages 693-697 (issn: 0960-8966, Copyright policy )
Country: Netherlands
tract We report a novel mitochondrial m.4414T>C variant in the mt-tRNAMet (MT-TM) gene in an adult patient with chronic progressive external ophthalmoplegia and myopathy whose muscle biopsy revealed focal cytochrome c oxidase (COX)-deficient and ragged red fibres. The m.4414T>C variant occurs at a strongly evolutionary conserved sequence position, disturbing a canonical base pair and disrupting the secondary and tertiary structure of the mt-tRNAMet. Definitive evidence of pathogenicity is provided by clear segregation of m.4414T>C mutant levels with COX deficiency in single muscle fibres. Interestingly, the variant is present in skeletal muscle at relatively low levels (30%) and undetectable in accessible, non-muscle tissues from the patient and her asymptomatic brother, emphasizing the continuing requirement for a diagnostic muscle biopsy as the preferred tissue for mtDNA genetic investigations of mt-tRNA variants leading to mitochondrial myopathy.
Subjects by Vocabulary

Microsoft Academic Graph classification: Muscle biopsy medicine.diagnostic_test medicine External ophthalmoplegia Molecular biology Mitochondrial myopathy medicine.disease Biology Mitochondrial disease Cytochrome c oxidase biology.protein Skeletal muscle medicine.anatomical_structure Chronic progressive external ophthalmoplegia Myopathy medicine.symptom


Mitochondrial disease, Chronic progressive external ophthalmoplegia, Myopathy, mtDNA variant, m.4414T>C, MTTM, MUTATION, ASSAY, Genetics (clinical), Neurology (clinical), Neurology, Pediatrics, Perinatology and Child Health