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The epsilon-sarcoglycan gene (SGCE), mutated in myoclonus-dystonia syndrome, is maternally imprinted

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http://pubman.mpdl.mpg.de/cone/persons/resource/persons50369

Kalscheuer,  Vera
Chromosome Rearrangements and Disease (Vera Kalscheuer), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Zitation

Grabowski, M., Zimprich, A., Lorenz-Depiereux, B., Kalscheuer, V., Asmus, F., Gasser, T., et al. (2003). The epsilon-sarcoglycan gene (SGCE), mutated in myoclonus-dystonia syndrome, is maternally imprinted. European Journal of Human Genetics, 11(2), 138-144. doi:10.1038/sj.ejhg.5200938.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0010-8AC6-3
Zusammenfassung
Myoclonus-dystonia syndrome (MDS) is a non-degenerative neurological disorder that has been described to be inherited in an autosomal dominant mode with incomplete penetrance. MDS is caused by loss of function mutations in the epsilon-sarcoglycan gene. Reinvestigation of MDS pedigrees provided evidence for a maternal imprinting mechanism. 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. Our findings revealed that in peripheral blood leukocytes the maternal allele is methylated, while the paternal allele is unmethylated. We also showed that most likely the maternal allele is completely methylated in brain tissue. Furthermore, CpG dinucleotides in maternal and paternal uniparental disomy 7 (UPD7) lymphoblastoid cell lines show a corresponding parent-of-origin specific methylation pattern. 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. These results provide strong evidence for a maternal imprinting of the SGCE gene. The inheritance pattern in MDS families is in agreement with such an imprinting mechanism with the exception of a few cases. We investigated one affected female that inherited the mutated allele from her mother. Surprisingly, we found the paternal wild type allele expressed whereas the mutated maternal allele was not detectable in peripheral blood cDNA.