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 (G AG) 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, tor sin A. TOR1A and its homologue TOR1B (alias DQ1) are located adjacent to ea ch other on human chromosome 9q34, Both genes comprise five similar exons; each gene spans a 10-kb region. Mutational analysis of most of the coding r egion and splice junctions of TOR1A and TOR1B did not reveal additional mut ations in typical early onset cases lacking the GAG deletion (N = 17), in d ystonic individuals with apparent homozygosity in the 9q34 chromosomal regi on (N = 5), or in a representative Ashkenazic Jewish individual with late o nset dystonia, who shared a common haplotype in the 9q34 region with other late onset individuals in this ethnic group. A database search revealed a f amily of nine related genes (50-70% similarity) and their orthologues in sp ecies including human, mouse, rat, pig, zebrafish, fruitfly, and nematode, At least four of these genes occur in the human genome. Proteins encoded by this gene family share functional domains with the AAA/HSP/Clp-ATPase supe rfamily of chaperone-like proteins, but appear to represent a distinct evol utionary branch. (C) 1999 Academic Press.