The TOR1A (DYT1) gene family and its role in early onset torsion dystonia.

Most cases of early onset torsion dystonia are caused by a 3-bp deletion (GAG) in the coding region of the TOR1A gene (alias DYT1, DQ2), resulting in loss of a glutamic acid in the carboxy terminal of the encoded protein, torsin A. TOR1A and its homologue TOR1B (alias DQ1) are located adjacent to each other on hu- man chromosome 9q34. Both genes comprise five sim- ilar exons; each gene spans a 10-kb region. Mutational analysis of most of the coding region and splice junc- tions of TOR1A and TOR1B did not reveal additional mutations in typical early onset cases lacking the GAG deletion (N 5 17), in dystonic individuals with appar- ent homozygosity in the 9q34 chromosomal region (N 5 5), or in a representative Ashkenazic Jewish in- dividual with late onset dystonia, who shared a com- mon haplotype in the 9q34 region with other late onset individuals in this ethnic group. A database search revealed a family of nine related genes (50 -70% simi- larity) and their orthologues in species including hu- man, mouse, rat, pig, zebrafish, fruitfly, and nematode. At least four of these genes occur in the human ge- nome. Proteins encoded by this gene family share functional domains with the AAA/HSP/Clp-ATPase su- perfamily of chaperone-like proteins, but appear to represent a distinct evolutionary branch. © 1999 Academic