Elsevier

Genomics

Volume 62, Issue 3, 15 December 1999, Pages 377-384
Genomics

Regular Article
The TOR1A (DYT1) Gene Family and Its Role in Early Onset Torsion Dystonia

https://doi.org/10.1006/geno.1999.6039Get rights and content

Abstract

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 human chromosome 9q34. Both genes comprise five similar exons; each gene spans a 10-kb region. Mutational analysis of most of the coding region and splice junctions of TOR1A and TOR1B did not reveal additional mutations in typical early onset cases lacking the GAG deletion (N = 17), in dystonic individuals with apparent homozygosity in the 9q34 chromosomal region (N = 5), or in a representative Ashkenazic Jewish individual with late onset dystonia, who shared a common 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% similarity) and their orthologues in species 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 superfamily of chaperone-like proteins, but appear to represent a distinct evolutionary branch.

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      Citation Excerpt :

      It has been reported that individuals with TOR1A mutations on only one allele may not show dystonic symptoms; explained by incomplete or reduced penetrance. For example, among carriers of predominant mutation (c.907_909delGAG) only 30% have been shown to be symptomatic (Ozelius et al., 1999). In the case presented here, the parents who carry heterozygous p.Arg288* variant did not show any dystonic symptoms consistent with reduced penetrance.

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    Present address: Department of Neurology, Medical University of Luebeck, 23538 Luebeck, Germany.

    1

    Present address: Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461.

    3

    Present address: Fukuoka-shi, Fukuoka, 810-0055 Japan.

    4

    To whom correspondence should be addressed at Department of Molecular Neurogenetics, Massachusetts General Hospital East, 13th Street, Building 149, Charlestown, MA 02129. Telephone: (617) 726-5728, Fax: (617) 724-1537. E-mail: [email protected].

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