Myoclonus-dystonia due to genomic deletions in the epsilon-sarcoglycan gene.

Direct genomic DNA sequencing fails to detect epsilon-sarcoglycan (SGCE) mutations in up to 30% of familial myoclonus-dystonia (M-D) cases. We identified novel large heterozygous deletions of SGCE exon 5 or exon 6 in two M-D pedigrees. Like nonsense mutations, exon rearrangements result in the generation of premature stop codons downstream of the deleted exon. SGCE exon dosage assays may identify additional families with SGCE mutation and thus reduce "genetic heterogeneity."