Table 1.

Summary of Molecular Genetic Testing Used in Myoclonus-Dystonia

Gene 1Test MethodPathogenic Variants Detected 2Variant Detection Frequency by Test Method 3
Familial 4Simplex 5, 6, 7
SGCESequence analysis 8Sequence variants 9~30%-50%~10%-15%
Deletion/duplication analysis 10Exon or whole-gene deletionsUnknown 11

See Table A. Genes and Databases for chromosome locus and protein.


See Molecular Genetics for information on allelic variants.


The ability of the test method used to detect a variant that is present in the indicated gene


The variant detection rate among familial cases ranges from 0% to 100% with the high range biased by linkage studies; on average, the overall rate based on the literature is close to 50%. The detection rate increases when there is paternal transmission [Zimprich et al 2001, Asmus et al 2002, Klein 2002, Müller et al 2002, Hjermind et al 2003, Maréchal et al 2003, Hedrich et al 2004, Schüle et al 2004, Valente et al 2005, Tezenas du Montcel et al 2006, Grünewald et al 2008, Nardocci et al 2008, Raymond et al 2008, Ritz et al 2009].


The variant detection rate among simplex cases (i.e., individuals with no family history of M-D) averages about 12%-13% overall [Asmus et al 2002, Han et al 2003, Valente et al 2003, Grundmann et al 2004, Hedrich et al 2004, Schüle et al 2004, Valente et al 2005, Tezenas du Montcel et al 2006].


85 pathogenic variants are listed in HGMD (see Table A. Genes and Databases); a few are confirmed de novo pathogenic variants [Nardocci et al 2008].


In two probands who appeared to represent simplex cases, the pathogenic variant was subsequently identified in the fathers [Müller et al 2002, Hedrich et al 2004, Kock et al 2004].


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


To date, the vast majority (~95%) of SGCE pathogenic variants have been found in exons 1-7; the remaining approximately 5% have been found in exon 9.


Testing that identifies exon or whole-gene deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; a variety of methods including quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), or targeted chromosomal microarray analysis (gene/segment-specific) may be used. A full chromosomal microarray analysis that detects deletions/duplications across the genome may also include this gene/segment.


Exon and whole-gene deletions are likely to account for a relatively small percentage of SGCE pathogenic variants [DeBerardinis et al 2003, Asmus et al 2005, Asmus et al 2007, Han et al 2007, Grünewald et al 2008, Ritz et al 2009].

From: Myoclonus-Dystonia

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