Analysis of TBX1 variation in patients with psychotic and affective disorders
Analysis of TBX1 variation in patients with psychotic and affective disorders
复制标题
DOI：
10.2119/2006-00119.funke
复制
发表时间：
2007-07-01
影响因子：
5.7
通讯作者：
Kucherlapati, Raju
中科院分区：
文献类型：
--
作者：
Funke, Birgit H.;Lencz, Todd;Kucherlapati, Raju
很大一部分22 q11缺失综合征（22 q11 DS）患者发展为精神障碍，包括精神分裂症和其他精神病性和情感性症状，并且假定相关基因在非综合征性精神疾病的病因学中也起重要作用。22 q11 DS患者中最常见的精神病诊断是精神分裂症，被认为是神经递质失衡和大脑发育紊乱的结果。在22 q11区域的几个已知或怀疑在神经递质代谢中起作用的基因已经在孤立的精神分裂症患者中进行了分析;然而，它们对疾病的贡献仍然存在争议，TBX 1基因的单倍不足已被证明足以导致小鼠和人类中与22 q 11 DS相关的核心身体畸形，并且通过异常的大脑发育可能导致22 q 11 DS。11 DS相关和孤立的精神疾病。22 q11 DS人群中精神分裂症以外的精神疾病的发病率也有所增加，包括情绪障碍。因此，我们分析了446例白色与22 q11 DS相关的精神疾病患者和436例种族匹配的对照组中TBX 1位点的变异。主要诊断包括精神分裂症（n = 226）、情感障碍（n = 67）、双相情感障碍（n = 82）和重度抑郁症（n = 29）。我们对该样本中的9个标签SNPs进行了基因分型，但与对照组相比，在任何分析组（所有受影响的精神分裂症和情感障碍，单独的精神分裂症，双相情感障碍和重度抑郁症）中均未观察到等位基因或单体型频率的显著差异。基于这些结果，我们得出结论，TBX 1变异并没有作出强有力的贡献，常见于22 q 11 DS患者的非综合征形式的精神疾病的遗传病因。
A significant portion of patients with 22q11 deletion syndrome (22q11 DS) develop psychiatric disorders, including schizophrenia and other psychotic and affective symptoms, and the responsible gene/s are assumed to also play a significant role in the etiology of nonsyndromic psychiatric disease. The most common psychiatric diagnosis among patients with 22q 11DS is schizophrenia, thought to result from neurotransmitter imbalances and also from disturbed brain development. Several genes in the 22q 11 region with known or suspected roles in neurotransmitter metabolism have been analyzed in patients with isolated schizophrenia; however, their contribution to the disease remains controversial, Haploinsufficiency of the TBX1 gene has been shown to be sufficient to cause the core physical malformations associated with 22q 11 DS in mice and humans and via abnormal brain development could contribute to 22q 11 DS-related and isolated psychiatric disease. 22q 11DS populations also have increased rates of psychiatric conditions other than schizophrenia, including mood disorders. We therefore analyzed variations at the TBX1 locus in a cohort of 446 white patients with psychiatric disorders relevant to 22q 11 DS and 436 ethnically matched controls, The main diagnoses included schizophrenia (n = 226), schizoaffective disorder (n = 67), bipolar disorder (n = 82), and major depressive disorder (n = 29). We genotyped nine tag SNPs in this sample but did not observe significant differences in allele or haplotype frequencies in any of the analyzed groups (all affected, schizophrenia and schizoaffective disorder, schizophrenia alone, and bipolar disorder and major depressive disorder) compared with the control group. Based on these results we conclude that TBX1 variation does not make a strong contribution to the genetic etiology of nonsyndromic forms of psychiatric disorders commonly seen in patients with 22q 11 DS.