Human Molecular Genetics, Vol 7, 1133-1136, Copyright © 1998 by Oxford University Press
C Klein, MF Brin, D de Leon, SA Limborska, IA Ivanova-Smolenskaya, SB Bressman, A Friedman, ED Markova, NJ Risch, XO Breakefield and LJ Ozelius
The DYT1 gene recently has been cloned and shown to contain a three
nucleotide (GAG) deletion responsible for most cases of autosomal dominant
early-onset torsion dystonia. This deletion results in the loss of one of a
pair of glutamic acids in a conserved region of a novel ATP-binding protein
(torsinA). Previous haplotype analysis revealed that this same deletion had
arisen at least two different times in history, suggesting independent
mutational events. This deletion is the only sequence change found thus far
to be associated uniquely with the disease status, regardless of ethnic
origin. Here we describe two patients with typical early-onset torsion
dystonia of Swiss-Mennonite and non-Jewish Russian origin, respectively,
that both carry this same mutation as a de novo GAG deletion. This finding
proves that this 3 bp deletion in the DYT1 gene is indeed a mutation that
causes early-onset torsion dystonia. The DYT1 mutation is one of the rare
examples of the same recurrent mutation causing a dominantly inherited
condition. The sequence surrounding the GAG deletion contains an imperfect
24 bp tandem repeat, suggesting a possible mechanism for the high frequency
of this mutation.
ARTICLES
De novo mutations (GAG deletion) in the DYT1 gene in two non-Jewish patients with early-onset dystonia
Molecular Neurogenetics Unit, Neurology Service, Massachusetts General Hospital and Department of Neurology and Genetics, Harvard Medical School, Boston, MA, USA.
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