De novo mutations (GAG deletion) in the DYT1 gene in two non-Jewish patients with early-onset dystonia

被引:58
作者
Klein, C
Brin, MF
de Leon, D
Limborska, SA
Ivanova-Smolenskaya, IA
Bressman, SB
Friedman, A
Markova, ED
Risch, NJ
Breakefield, XO
Ozelius, LJ [1 ]
机构
[1] Massachusetts Gen Hosp, Neurol Serv, Mol Neurogenet Unit, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Dept Neurol & Genet, Boston, MA USA
[3] Mt Sinai Hosp, Dept Neurol, Movement Disorders Ctr, New York, NY 10029 USA
[4] Columbia Presbyterian Med Ctr, Dept Neurol, Dystoria Clin Res Ctr, New York, NY 10032 USA
[5] Russian Acad Sci, Inst Mol Genet, Moscow 123182, Russia
[6] Inst Neurol, Moscow, Russia
[7] Stanford Univ, Dept Genet, Stanford, CA 94305 USA
[8] Med Acad Warsaw, Dept Neurol, Warsaw, Poland
关键词
D O I
10.1093/hmg/7.7.1133
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 nonJewish 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.
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收藏
页码:1133 / 1136
页数:4
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