Document Detail

Genome-wide analysis shows association of epigenetic changes in regulators of Rab and Rho GTPases with spinal muscular atrophy severity.
MedLine Citation:
PMID:  23299920     Owner:  NLM     Status:  MEDLINE    
Spinal muscular atrophy (SMA) is a monogenic disorder that is subdivided into four different types and caused by survival motor neuron gene 1 (SMN1) deletion. Discordant cases of SMA suggest that there exist additional severity modifying factors, apart from the SMN2 gene copy number. Here we performed the first genome-wide methylation profiling of SMA patients and healthy individuals to study the association of DNA methylation status with the severity of the SMA phenotype. We identified strong significant differences in methylation level between SMA patients and healthy controls in CpG sites close to the genes CHML, ARHGAP22, CYTSB, CDK2AP1 and SLC23A2. Interestingly, the CHML and ARHGAP22 genes are associated with the activity of Rab and Rho GTPases, which are important regulators of vesicle formation, actin dynamics, axonogenesis, processes that could be critical for SMA development. We suggest that epigenetic modifications may influence the severity of SMA and that these novel genetic positions could prove to be valuable biomarkers for the understanding of SMA pathogenesis.
Galina Y Zheleznyakova; Sarah Voisin; Anton V Kiselev; Markus Sällman Almén; Miguel J Xavier; Marianna A Maretina; Lyudmila I Tishchenko; Robert Fredriksson; Vladislav S Baranov; Helgi B Schiöth
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-09
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  21     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-08-16     Completed Date:  2014-03-24     Revised Date:  2014-09-02    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  988-93     Citation Subset:  IM    
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MeSH Terms
Case-Control Studies
Child, Preschool
CpG Islands
DNA Methylation
Epigenesis, Genetic*
Gene Ontology
Genetic Predisposition to Disease
Genome-Wide Association Study
Muscular Atrophy, Spinal / genetics*,  pathology
Sequence Analysis, DNA
Young Adult
rab GTP-Binding Proteins / genetics*,  metabolism
rho GTP-Binding Proteins / genetics*,  metabolism
Reg. No./Substance:
EC 3.6.1.-/rab GTP-Binding Proteins; EC GTP-Binding Proteins

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