We investigate the molecular and cellular etiologies that underlie the deletion of the six amino acid residues (?F323-Y328; ?FY) in human torsin A (HtorA). The most common and severe mutation involved with early-onset torsion dystonia is a glutamic acid deletion (?E 302/303; ?E) in HtorA which induces protein aggregates in neurons and cells. Even though ?FY HtorA forms no protein clusters, flies expressing ?FY HtorA in neurons or muscles manifested a similar but delayed onset of adult locomotor disability compared with flies expressing ?E in HtorA. In addition, flies expressing ?FY HtorA had fewer aberrant ultrastructures at synapses compared with flies expressing ?E HtorA. Taken together, the ?FY mutation in HtorA may be responsible for behavioral and anatomical aberrations in Drosophila.

Keywords: disorders, dystonia, DYT1, movement, synapse