Clinical and myopathological characteristics of desminopathy caused by a mutation in desmin tail domain

Paul Maddison, Maxwell S Damian, Caroline Sewry, Catherine McGorrian, John B Winer, Zagaa Odgerel, Alexey Shatunov, Hee Suk Lee, Lev G Goldfarb

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)


    BACKGROUND: Most of the previously described pathogenic mutations in desmin are located in highly conserved α-helical domains that play an important role in intermediate filament assembly. The role of the C-terminus non-α-helical 'tail' domain is much less investigated and until recently mutations in this domain have been implicated in only a few patients. The majority of reported desminopathy cases caused by the tail mutations were sporadic, creating a representation bias regarding the disease frequency and phenotypic characteristics.

    METHODS: We performed detailed genotype-phenotype analysis of autosomal dominant desminopathy associated with tail domain mutations in a four-generation autosomal dominant family with 16 members affected by a progressive cardiac and/or skeletal myopathy caused by a c.1346A>C (p.Lys449Thr) mutation located in the tail domain of desmin.

    RESULTS: Phenotypic features in patients with tail domain mutations are similar to those in patients with mutations localized in the 1B and 2B α-helical domains.

    CONCLUSION: We recommend that the tail domain is searched for mutations as intensely as desmin coil domains which until recently were considered to be more 'functional'.

    Original languageEnglish
    Pages (from-to)279-286
    Number of pages8
    JournalEuropean Neurology
    Issue number5
    Publication statusPublished - Nov 2012


    • Adult
    • Aged
    • Desmin
    • Female
    • Humans
    • Intermediate Filaments
    • Male
    • Middle Aged
    • Muscular Diseases
    • Mutation
    • Pedigree
    • Journal Article
    • Research Support, N.I.H., Intramural


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