Department of Medical Genetics, Institute of Human Genetics, University of Tuebingen, Tuebingen, Germany.
Neurobiol Dis. 2010 May;38(2):192-200. doi: 10.1016/j.nbd.2009.12.019. Epub 2010 Jan 4.
DYT1 dystonia is an autosomal-dominantly inherited movement disorder, which is usually caused by a GAG deletion in the TOR1A gene. Due to the reduced penetrance of approximately 30-40%, the determination of the mutation in a subject is of limited use with regard to actual manifestation of symptoms. In the present study, we used Affymetrix oligonucleotide microarrays to analyze global gene expression in blood samples of 15 manifesting and 15 non-manifesting mutation carriers in order to identify a susceptibility profile beyond the GAG deletion which is associated with the manifestation of symptoms in DYT1 dystonia. We identified a genetic signature which distinguished between asymptomatic mutation carriers and symptomatic DYT1 patients with 86.7% sensitivity and 100% specificity. This genetic signature could correctly predict the disease state in an independent test set with a sensitivity of 87.5% and a specificity of 85.7%. Conclusively, this genetic signature might provide a possibility to distinguish DYT1 patients from asymptomatic mutation carriers.
DYT1 型肌张力障碍是一种常染色体显性遗传运动障碍，通常由 TOR1A 基因中的 GAG 缺失引起。由于大约 30-40%的外显率降低，因此在确定受检者的突变时，对于症状的实际表现，其作用有限。在本研究中，我们使用 Affymetrix 寡核苷酸微阵列分析了 15 名有症状和 15 名无症状突变携带者的血液样本中的全基因组表达，以确定与 DYT1 型肌张力障碍症状表现相关的除 GAG 缺失之外的易感性特征。我们发现了一个遗传特征，可以区分无症状突变携带者和有症状的 DYT1 患者，其敏感性为 86.7%，特异性为 100%。该遗传特征在独立的测试集中可以正确预测疾病状态，敏感性为 87.5%，特异性为 85.7%。总之，该遗传特征可能为区分 DYT1 患者和无症状突变携带者提供了一种可能。
