Expression profiling in peripheral blood reveals signature for penetrance in DYT1 dystonia.
Expression profiling in peripheral blood reveals signature for penetrance in DYT1 dystonia.
复制标题
外周血中的表达谱揭示了 DYT1 肌张力障碍的外显率特征。
DOI：
10.1016/j.nbd.2009.12.019
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发表时间：
2010
影响因子：
6.1
通讯作者：
Grundmann,K
中科院分区：
文献类型：
--
作者：
Walter,M;Bonin,M;Pullman,RSaunders;Valente,EM;Loi,M;Gambarin,M;Raymond,D;Tinazzi,M;Kamm,C;Glöckle,N;Poths,S;Gasser,T;Bressman,SB;Klein,C;Ozelius,LJ;Riess,O;Grundmann,K
DYT 1肌张力障碍是一种常染色体显性遗传的运动障碍，通常由TOR 1A基因中的GAG缺失引起。由于突变率降低了30 - 40%，在受试者中确定突变对于症状的实际表现的用途有限。在本研究中，我们使用了Affyrin寡核苷酸微阵列分析全球基因表达的血液样本中的15个表现和15个非表现突变载体，以确定超出GAG缺失的易感性，这是与DYT1肌张力障碍的症状表现。我们确定了一个基因签名，区分无症状的突变携带者和有症状的DYT1患者，敏感性为86.7%，特异性为100%。该基因签名可以在独立测试集中正确预测疾病状态，灵敏度为87.5%，特异性为85.7%。总之，这种基因签名可能提供区分DYT1患者与无症状突变携带者的可能性。
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 ∼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.