Disease relevance of SGCE

• Myoclonus-dystonia syndrome (MDS; DYT11) is an autosomal dominant disorder characterized by bilateral, alcohol-sensitive myoclonic jerks involving mainly the arms and axial muscles [1].
• Myoclonus-dystonia (M-D) is a movement disorder characterized by rapid muscle contractions and sustained twisting and repetitive movements and has recently been associated with mutations in the epsilon-sarcoglycan gene (SGCE) [2].
• These included 72 controls (C), 659 early and suspect open angle glaucoma (ESG) with perimetric mean defect (MD) lower than 6 dB, and 242 confirmed moderate and advanced glaucomas (AG) with perimetric MD >/=6 dB [3].

Psychiatry related information on SGCE

• Examination of the SGCE gene in Tourette syndrome patients with obsessive-compulsive disorder [4].

High impact information on SGCE

• Loss of imprinting in the patient with M-D who had biallelic expression of the SGCE gene was associated with partial loss of methylation at several CpG dinucleotides [2].
• In addition, we identified differentially methylated regions in the promoter region of the SGCE gene as a characteristic feature of imprinted genes [2].
• SGCE missense mutations that cause myoclonus-dystonia syndrome impair {varepsilon}-sarcoglycan trafficking to the plasma membrane: modulation by ubiquitination and torsinA [5].
• These data demonstrate that some MDS-associated mutations in SGCE impair trafficking of the mutant protein to the plasma membrane and suggest a role for torsinA and the ubiquitin proteasome system in the recognition and processing of misfolded epsilon-sarcoglycan [5].
• SGCE is a maternally imprinted gene with the disease being inherited in an autosomal dominant pattern with reduced penetrance upon maternal transmission [5].

Biological context of SGCE

• Suitable mutation negative families were tested for linkage to the SGCE region and to chromosome 18p11 [6].
• To determine the contribution of mutations in the SGCE gene in patients with different subtypes of dystonias, we analyzed the coding sequence of the SGCE gene in a group of 296 patients with a clinical phenotype of primary dystonia and in 2 patients with a clinical phenotype of myoclonus-dystonia [7].
• SGCE exon dosage assays may identify additional families with SGCE mutation and thus reduce "genetic heterogeneity."[8]
• The epsilon-sarcoglycan gene (SGCE) on human chromosome 7q21 has been reported to be a major locus for inherited myoclonus-dystonia [9].
• All coding exons of the SGCE gene were analysed [10].

Anatomical context of SGCE

• The effect of differential methylation on the expression of the SGCE gene was tested in UPD7 cell lines with only a weak RT-PCR signal observed in matUPD7 and a strong signal in patUPD7 [11].
• An 8-year-old boy presenting with early onset, medically intractable, MDS due to a mutation in the epsilon-sarcoglycan gene (SGCE) underwent chronic bilateral stimulation of the globus pallidus internus, which eliminates both myoclonus and dystonia [12].
• By RNA analysis, we observed expression of alpha-, beta-, gamma-, delta-, epsilon-SG, and SSPN in smooth muscle cells [13].
• In endothelial cells, immunostaining only evidenced the presence of epsilon-SG and SSPN [13].

Associations of SGCE with chemical compounds

• RESULTS: Distinct truncating mutations in the SGCE gene were identified in each family [14].
• Autosomal dominant alcohol-responsive M-D is associated with mutations in the epsilon-sarcoglycan gene (SGCE) (six families) and with a missense change in the D2 dopamine receptor (DRD2)gene (one family) [14].

Other interactions of SGCE

• PEG10 is located near the SGCE (Sarcoglycan epsilon) gene, whose mouse homologue was recently shown to be imprinted [15].
• Our results suggest that mutations in the SGCE gene cannot be held responsible for other subtypes of primary dystonia [7].
• As differential methylated regions (DMRs) are a characteristic feature of imprinted genes, we studied the methylation pattern of CpG dinucleotides within the CpG island containing the promoter region and the first exon of the SGCE gene by bisulphite genomic sequencing [11].
• Additionally, we observed an increment in the protein levels of epsilon-SG, beta-DG, UTR and cav-1 after mechanical stretching [16].

Analytical, diagnostic and therapeutic context of SGCE

• We used fluorescence in situ hybridization (FISH) to estimate the size of our patient's deletion (9.0-15 Mbp) and to confirm absence of SGCE on the affected chromosome [17].
• Polymerase chain reaction (PCR) analysis of polymorphic markers in the region revealed that the paternally inherited chromosome contained the deletion, consistent with a model of maternal SGCE imprinting [17].

References