Evidence that paternal expression of the ε-Sarcoglycan gene accounts for reduced penetrance in myoclonus-dystonia

Birgitt Müller, Katja Hedrich, Norman Kock, Natasa Dragasevic, Marina Svetel, Jennifer Garrels, Olfert Landt, Matthias Nitschke, Peter P. Pramstaller, Wolf Reik, Eberhard Schwinger, Jürgen Sperner, Laurie Ozelius, Vladimir Kostic, Christine Klein*

*Corresponding author for this work
103 Citations (Scopus)


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 ∈-sarcoglycan gene (SGCE). The mode of inheritance is autosomal dominant with reduced penetrance upon maternal transmission, suggesting a putative maternal imprinting mechanism. We present an apparently sporadic M-D case and two patients from an M-D family with seemingly autosomal recessive inheritance. In both families, we detected an SGCE mutation that was inherited from the patients' clinically unaffected fathers in an autosomal dominant fashion. Whereas, in the first family, RNA expression studies revealed expression of only the mutated allele in affected individuals and expression of the normal allele exclusively in unaffected mutation carriers, the affected individual of the second family expressed both alleles. In addition, we identified differentially methylated regions in the promoter region of the SGCE gene as a characteristic feature of imprinted genes. Using a rare polymorphism in the promoter region in a family unaffected with M-D as a marker, we demonstrated methylation of the maternal allele, in keeping with maternal imprinting of the SGCE gene. 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.

Original languageEnglish
JournalAmerican Journal of Human Genetics
Issue number6
Pages (from-to)1303-1311
Number of pages9
Publication statusPublished - 01.12.2002


Dive into the research topics of 'Evidence that paternal expression of the ε-Sarcoglycan gene accounts for reduced penetrance in myoclonus-dystonia'. Together they form a unique fingerprint.

Cite this