Abstract Details

Title Major Role of CUGBP1 in Classic Adult DM1 but Not in DM2

Topic Muscle Disease/Neuromuscular Junction

Presentation(s) (-)

Poster/Presentation
Number 006

Objective

Background Myotonic dystrophy (DM) is a multisystemic disease affecting mainly skeletal muscle, heart, and the central nervous system. Two DM loci are associated with the disease: DM1 caused by the expansion of an unstable CTG repeat in the 3[prime] UTR of DMPK gene and DM2 caused by the expansion of an unstable CCTG expansion in the first intron of the CNBP gene. Mutant RNA transcripts accumulate in ribonuclear inclusions interfering with the localization or expression of specific RNA-binding proteins such as MBNL1 and CUGBP1, resulting in spliceopathy of downstream effector genes. The prevailing paradigm therefore is that both disorders are toxic RNA disease. The role of CUGBP1 is particularly intriguing since contradictory results on its expression in DM2 muscles have been reported.

Design/Methods This study has been conducted on biceps brachii of DM1 (n=11), DM2 (n=14) patients and controls (n=8). CUGBP1and CNBP protein expressions and the alternative splicing of CLCN1, IR, SERCA1 and MBNL1 genes has been correlated to presenting phenotypes (mild-E1 vs classic-E2 vs CDM in DM1 and PROMM vs PDM vs paucisymptomatic in DM2).

Results An increase of CUGBP1 expression has been observed only in DM1-E2 but not in CDM, DM1-E1 and DM2 muscles. CNBP expression is significantly lower in DM2 than in DM1 and control muscles. Spliceopathy is evident in both DM1 and DM2 muscles despite the clinical phenotype. Moreover it appears that DM1-E1 and DM2-paucisymptomatic patients with less severe phenotype show a milder spliceopathy profile than that observed in the other DM patients considered.

Conclusions Our results indicate that CUGBP1 seems play a major role in classic adult DM1 but not in DM2 thus confirming that, beyond spliceopathy, other factors, such as CUGBP1, take place with respect to pathomolecular mechanism of disease-specific manifestations.

Authors/Disclosures
Giovanni Meola, MD, FAAN PRESENTER	No disclosure on file
	No disclosure on file
Ugur Uygunoglu (Cerrahpasa)	Ugur Uygunoglu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Turkey . The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen Idec/Gen Pharma of Turkey. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck-Serono of Turkey. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanovel of Turkey. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Genveon of Turkey.
	No disclosure on file
	No disclosure on file
	No disclosure on file

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