Abnormal expression of dysferlin in skeletal muscle and monocytes supports primary dysferlinopathy in patients with one mutated allele

M. Meznaric, L. Gonzalez-Quereda, E. Gallardo, N. de Luna, P. Gallano, M. Fanin, C. Angelini, B. Peterlin, J. Zidar

    Research output: Contribution to journalArticleResearchpeer-review

    14 Citations (Scopus)

    Abstract

    Background: In some cases, a definitive confirmation of dysferlinopathy cannot be achieved by DNA test, because the mutation is detected in one allele only. Patients and methods: Dysferlin expression in skeletal muscle and peripheral blood monocytes (PBM) was studied by Western blot in two unrelated adult patients. The comparative CT method (ΔΔCT) was used to calculate relative changes in dysferlin mRNA determined from real-time quantitative PCR experiments. The dysferlin gene was studied by direct sequencing of cDNA and genomic DNA and by Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. Results: A comparable severe reduction in dysferlin was demonstrated in both skeletal muscle and PBM. The expression of dysferlin mRNA was significantly reduced. A novel mutation in exon 47 (c.5289G>C) of the dysferlin gene in the heterozygous state, causing an amino acid change (p.Glu1763Asp), was detected in both patients. The MLPA analysis did not reveal any deletion or duplication. Conclusions: Dysferlin and/or dysferlin mRNA abnormalities are diagnostic for dysferlinopathy when mutational analysis detects a mutation in one allele only. Analysis of dysferlin mRNA can be helpful for distinguishing symptomatic heterozygotes from such patients. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.
    Original languageEnglish
    Pages (from-to)1021-1023
    JournalEuropean Journal of Neurology
    Volume18
    Issue number7
    DOIs
    Publication statusPublished - 1 Jan 2011

    Keywords

    • Dysferlin mRNA
    • Dysferlinopathy
    • Heterozygous state
    • Miyoshi myopathy

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