A subgroup of Tourette's patients overexpress specific natural killer cell genes in blood: A preliminary report
A subgroup of Tourette's patients overexpress specific natural killer cell genes in blood: A preliminary report
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DOI：
10.1002/ajmg.b.30550
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发表时间：
2007-10-05
影响因子：
2.8
通讯作者：
Sharp, Frank R.
中科院分区：
文献类型：
--
作者：
Lit, Lisa;Gilbert, Donald L.;Sharp, Frank R.
抽动秽语综合征（TS）是一种遗传性神经发育障碍，其特征是运动和声音联系。由于没有单一基因或区域从标准连锁方法中出现，TS可能是由几个尚未确定的遗传因素引起的，也可能是由于感染触发的自身免疫过程而发生的。病因或致病性差异可能导致临床上难以区分的TS亚组。我们以前曾使用全基因组人类寡核苷酸微阵列，试图确定与TS血液中的基因表达模式。在这项原理验证研究中，我们将主成分分析应用于先前收集的16个家族性TS和16个对照血液样本，以确定亚组。14个基因，主要是自然杀伤细胞（NK）基因，区分TS和所有对照。采用RT-PCR法对颗粒酶B和NKG 7进行了鉴定。五个探针组（四个基因）位于先前与家族性TS或强迫症相关的染色体区域。使用这14个基因，主成分分析以及聚类分析鉴定了过表达NK基因的TS亚组（n = 10/ 16）。该亚组中7/10的受试者被诊断为注意力缺陷多动障碍（ADHD），这表明该表达谱可能与TS和共病ADHD相关。血液中基因表达的主成分分析可能有助于识别其他复杂神经发育疾病的亚组，本研究中确定的基因表达谱可能为至少一个遗传性TS亚组提供生物标志物。(c)2007 Wiley-Liss，Inc.
Gilles de la Tourette Syndrome (TS) is a heritable, neurodevelopmental disorder characterized by motor and vocal ties. As no single gene or region has emerged from standard linkage approaches, TS may result from several as-yet-unidentified genetic factors, and may also occur due to infection-triggered, autoimmune processes. Etiological or pathogenic differences might result in clinically indistinguishable TS subgroups. We have previously used whole genome human oligonucleotide microarrays in an attempt to identify patterns of gene expression in blood linked with TS. In this proof-of-principle study, we applied Principal Components Analysis to a previously collected set of 16 familial TS and 16 control blood samples to identify subgroups. Fourteen genes, primarily Natural Killer Cell (NK) genes, discriminated between TS and all controls. Granzyme B and NKG7 were confirmed using RT-PCR. Five probesets (four genes) reside in chromosomal regions previously linked to familial TS or obsessive-compulsive disorder. Using the 14 genes, a Principal Components Analysis as well as a cluster analysis identified a TS subgroup (n = 10/ 16) that overexpressed the NK genes. 7/10 subjects within this subgroup were diagnosed with attention-deficit hyperactivity disorder (ADHD), suggesting that this expression profile might be associated with TS and co-morbid ADHD. Principal Components Analysis of gene expression in blood may be useful for identifying subgroups of other complex neurodevelopmental diseases, and the gene expression profile identified in this study may provide a biomarker for at least one subgroup of heritable TS. (c) 2007 Wiley-Liss, Inc.