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PMID: 17708420 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Gene expression analysis in myotonic dystrophy: indications for a common molecular pathogenic pathway in DM1 and DM2.

Gene expression ·Vol. 13 ·No. 6 ·2007-00-00 ·Pages 339-51

Botta A, Vallo L, Rinaldi F, Bonifazi E, Amati F, Biancolella M, Gambardella S, Mancinelli E, Angelini C, Meola G, Novelli G

Abstract

An RNA gain-of-function of expanded transcripts is the most accredited molecular mechanism for myotonic dystrophy type 1 (DM1) and 2 (DM2). To disclose molecular parallels and divergences in pathogenesis of both disorders, we compared the expression profile of muscle biopsies from DM1 and DM2 patients to controls. DM muscle tissues showed a reduction in the major skeletal muscle chloride channel (CLCN1) and transcription factor Sp1 transcript levels and an abnormal processing of the CLCN1 and insulin receptor (IR) pre-mRNAs. No essential differences were observed in the muscle blind-like gene (MBNL1) and CUG binding protein 1 (CUGBP1) transcript levels as well as in the splicing pattern of the myotubularin-related 1 (MTMR1) gene. Macroarray analysis of 96 neuroscience-related genes revealed a considerable similar expression profile between the DM samples, reflective of a common muscle pathology origin. Using a twofold threshold, we found six misregulated genes important in calcium and potassium metabolism and in mitochondrial functions. Our results indicate that the DM1 and DM2 overlapping clinical phenotypes may derive from a common trans acting mechanism that traps and influences shared genes and proteins. An RNA gain-of-function of expanded transcripts is the most accredited molecular mechanism for myotonic dystrophy type 1 (DM1) and 2 (DM2). To disclose molecular parallels and divergences in pathogenesis of both disorders, we compared the expression profile of muscle biopsies from DM1 and DM2 patients to controls. DM muscle tissues showed a reduction in the major skeletal muscle chloride channel (CLCN1) and transcription factor Sp1 transcript levels and an abnormal processing of the CLCN1 and insulin receptor (IR) pre-mRNAs. No essential differences were observed in the muscle blind-like gene (MBNL1) and CUG binding protein 1 (CUGBP1) transcript levels as well as in the splicing pattern of the myotubularin-related 1 (MTMR1) gene. Macroarray analysis of 96 neuroscience-related genes revealed a considerable similar expression profile between the DM samples, reflective of a common muscle pathology origin. Using a twofold threshold, we found six misregulated genes important in calcium and potassium metabolism and in mitochondrial functions. Our results indicate that the DM1 and DM2 overlapping clinical phenotypes may derive from a common trans acting mechanism that traps and influences shared genes and proteins.

MeSH Terms
Adult Alternative Splicing Biopsy Chloride Channels/genetics Female Gene Expression Profiling Gene Expression Regulation Genes, MHC Class II Humans Ion Channels/genetics Male Muscles/metabolism,pathology Myotonic Dystrophy/classification,genetics,metabolism,pathology Oligonucleotide Array Sequence Analysis Protein Tyrosine Phosphatase, Non-Receptor Type 1 Protein Tyrosine Phosphatases/genetics,metabolism Protein Tyrosine Phosphatases, Non-Receptor Signal Transduction/genetics
Chemicals
CLC-1 channel Chloride Channels Ion Channels MTMR1 protein, human Protein Tyrosine Phosphatase, Non-Receptor Type 1 Protein Tyrosine Phosphatases Protein Tyrosine Phosphatases, Non-Receptor
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Botta Annalisa
Department of Biopathology, Tor Vergata University of Rome, Rome, Italy. abottait@yahoo.it
Vallo Laura
Rinaldi Fabrizio
Bonifazi Emanuela
Amati Francesca
Biancolella Michela
Gambardella Stefano
Mancinelli Enzo
Angelini Corrado
Meola Giovanni
Novelli Giuseppe
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Article Info
Journal
Gene expression
Abbr.
Gene Expr
ISSN
1052-2166
DOI
10.3727/000000006781510705
Email
abottait@yahoo.it
Published
2007-00-00
Pages
339-51
Language
English
Region
United States
NLM ID
9200651
PMCID
PMC6032453
Subset
IM
External Links
PubMed source DOI: 10.3727/000000006781510705 PMC Full Text View journal details
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