Disease progression in myotonic dystrophy type 2: histopathological and molecular parameters from muscle biopsies

M. Giagnacovo; R. Cardani; G. Meola

doi:10.4081/microscopie.2012.4982

Authors

M. Giagnacovo
marzia.giagnacovo@unipv.it
Dipartimento di Biologia e Biotecnologie “Lazzaro Spallanzani”, Laboratorio di Biologia cellulare e Neurobiologia, Università di Pavia, Pavia, Italy.
R. Cardani Laboratorio di Istopatologia Muscolare e Biologia Molecolare, IRCCS Policlinico San Donato, Università degli Studi di Milano, Milano; Fondazione Malattie Miotoniche-FMM Milano, Milano, Italy.
G. Meola Laboratorio di Istopatologia Muscolare e Biologia Molecolare, IRCCS Policlinico San Donato, Università degli Studi di Milano, Milano; Dipartimento di Neurologia, IRCCS Policlinico San Donato, Università degli Studi di Milano, Milano, Italy.

Myotonic dystrophy type 2 (DM2) is a dominantly inherited autosomal disease with multisystemic clinical features and is caused by expansion of a CCTG tetranucleotide repeat in the first intron of the zinc finger protein 9 (ZNF9) gene in 3q21. The expanded- CCUG-containing transcripts are retained in cell nuclei, as ribonuclear inclusions, which specifically sequester some splicing factors (as MBNL1), thus causing a general alteration of the pre-mRNA post-transcriptional pathway that is likely responsible for the DM2 multifactorial phenotype. DM2 is a disease of type 2 fibers and it is has been hypothesized that the symptom worsening that occurs with aging may be caused by the progressive accumulation of CCUG-expansion and the sequestration of protein factors. Thus, we carried out a morphometric analysis of ribonuclear inclusions and MBNL1 foci in muscle sections from three DM2 patients who underwent two successive biopsies, and we studied the evolution of the histopathological features. Increase in size and fluorescence intensity has been observed in MBNL1 foci, together with a worsening of muscle histopathological traits, such as type 2 fibers impairment.

Giagnacovo, M., Cardani, R., & Meola, G. (2012). Disease progression in myotonic dystrophy type 2: histopathological and molecular parameters from muscle biopsies. Microscopie, 17(1), 42–49. https://doi.org/10.4081/microscopie.2012.4982

Download Citation

PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.

An Open Access Publication is one that meets the following two conditions:

the author(s) and copyright holder(s) grant(s) to all users a free, irrevocable, worldwide, perpetual right of access to, and a license to copy, use, distribute, transmit and display the work publicly and to make and distribute derivative works, in any digital medium for any responsible purpose, subject to proper attribution of authorship, as well as the right to make small numbers of printed copies for their personal use.
a complete version of the work and all supplemental materials, including a copy of the permission as stated above, in a suitable standard electronic format is deposited immediately upon initial publication in at least one online repository that is supported by an academic institution, scholarly society, government agency, or other well-established organization that seeks to enable open access, unrestricted distribution, interoperability, and long-term archiving.

Authors who publish with this journal agree to the following terms:

Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.