Incomplete nonsense-mediated decay facilitates detection of a multi-exonic deletion mutation in SGCE.

Mutations in SGCE represent the major cause of the myoclonus-dystonia syndrome (DYT11), an autosomal dominant disorder of reduced penetrance. Virtually all affected individuals have myoclonus, which is concentrated in the upper extremities, neck and trunk. Over half of patients have dystonia, usually affecting the neck or arms. SGCE is maternally imprinted. Of the more than 70 SGCE mutations reported in the literature, 18 are large deletions disrupting at least one exon. Therefore, testing for exonic deletions should be considered in individuals with a classic phenotype in whom Sanger sequencing is unrevealing. However, standard methodologies for detection of exonic deletion mutations are expensive, labor intensive and can produce false negatives. Herein, we report the use of cDNA derived from leukocyte RNA to identify a deletion mutation (exons 4 and 5) of SGCE in a family with DYT11. Residual RNA from incomplete nonsense-mediated decay permitted reverse transcription to cDNA. Breakpoints of the 8939 bp heterozygous deletion were then defined with long-range polymerase chain reaction and Sanger sequencing. Use of cDNA generated by reverse transcription of leukocyte RNA can reduce the costs associated with diagnostic genetic testing and can facilitate detection of deletion mutations.