Different Molecular Signatures in Magnetic Resonance Imaging-staged Facioscapulohumeral Muscular Dystrophy Muscles

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Jun 22

PMID 22719944

Citations 62

Authors

Giorgio Tasca

Mario Pescatori

Mauro Monforte

Massimiliano Mirabella

Elisabetta Iannaccone

Roberto Frusciante

Tiziana Cubeddu

Francesco Laschena

Pierfrancesco Ottaviani

Enzo Ricci

Affiliations

Soon will be listed here.

Abstract

Background: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies and is characterized by a non-conventional genetic mechanism activated by pathogenic D4Z4 repeat contractions. By muscle Magnetic Resonance Imaging (MRI) we observed that T2-short tau inversion recovery (T2-STIR) sequences identify two different conditions in which each muscle can be found before the irreversible dystrophic alteration, marked as T1-weighted sequence hyperintensity, takes place. We studied these conditions in order to obtain further information on the molecular mechanisms involved in the selective wasting of single muscles or muscle groups in this disease.

Methods: Histopathology, gene expression profiling and real time PCR were performed on biopsies from FSHD muscles with different MRI pattern (T1-weighted normal/T2-STIR normal and T1-weighted normal/T2-STIR hyperintense). Data were compared with those from inflammatory myopathies, dysferlinopathies and normal controls. In order to validate obtained results, two additional FSHD samples with different MRI pattern were analyzed.

Results: Myopathic and inflammatory changes characterized T2-STIR hyperintense FSHD muscles, at variance with T2-STIR normal muscles. These two states could be easily distinguished from each other by their transcriptional profile. The comparison between T2-STIR hyperintense FSHD muscles and inflammatory myopathy muscles showed peculiar changes, although many alterations were shared among these conditions.

Conclusions: At the single muscle level, different stages of the disease correspond to the two MRI patterns. T2-STIR hyperintense FSHD muscles are more similar to inflammatory myopathies than to T2-STIR normal FSHD muscles or other muscular dystrophies, and share with them upregulation of genes involved in innate and adaptive immunity. Our data suggest that selective inflammation, together with perturbation in biological processes such as neoangiogenesis, lipid metabolism and adipokine production, may contribute to the sequential bursts of muscle degeneration that involve individual muscles in an asynchronous manner in this disease.

Citing Articles

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Meta-analysis towards FSHD reveals misregulation of neuromuscular junction, nuclear envelope, and spliceosome.

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FSHD muscle shows perturbation in fibroadipogenic progenitor cells, mitochondrial function and alternative splicing independently of inflammation.

Engquist E, Greco A, Joosten L, van Engelen B, Zammit P, Banerji C Hum Mol Genet. 2023; 33(2):182-197.

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Ragozzino E, Bortolani S, Di Pietro L, Papait A, Parolini O, Monforte M Acta Neuropathol Commun. 2023; 11(1):165.

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