Identification and characterization of the novel m.8305C>T MTTK and m.4440G>A MTTM gene mutations causing mitochondrial myopathies

Mauro Scarpelli, Lidia Carreño-Gago, Anna Russignan, Noemi de Luna, Clara Carnicer-Cáceres, Alessandra Ariatti, Lorenzo Verriello, Grazia Devigili, Paola Tonin, Elena Garcia-Arumi, Tomàs Pinós

    Research output: Contribution to journalArticleResearchpeer-review

    4 Citations (Scopus)

    Abstract

    © 2017 Elsevier B.V. We report on two novel mtDNA mutations in patients affected with mitochondrial myopathy. The first patient, a 44-year-old woman, had bilateral eyelid ptosis and the m.8305C>T mutation in the MTTK gene. The second patient, a 56-year-old man, had four-limb muscle weakness and the MTTM gene m.4440G>A mutation. Muscle biopsies in both patients showed ragged red fibers and numerous COX-negative fibers as well as a combined defect of complex I, III and IV activities. The two mutations were heteroplasmic and detected only in muscle tissue, with a higher mutation load in COX-negative fibers. Additionally, both mutations occurred in highly conserved mt-tRNA sites, and were not found by an in silico search in 30,589 human mtDNA sequences. Our report further expands the mutational and phenotypic spectrum of diseases associated with mutations in mitochondrial tRNA genes and reinforces the notion that mutations in mitochondrial tRNAs represent hot spots for mitochondrial myopathies in adults.
    Original languageEnglish
    Pages (from-to)137-143
    JournalNeuromuscular Disorders
    Volume28
    Issue number2
    DOIs
    Publication statusPublished - 1 Feb 2018

    Keywords

    • Mitochondrial diseases
    • Myopathy
    • PEO
    • mtDNA

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