Rare NRXN1 promoter variants in patients with schizophrenia.
Rare NRXN1 promoter variants in patients with schizophrenia.
复制标题
精神分裂症患者中罕见的 NRXN1 启动子变异。
DOI：
10.1016/j.neulet.2010.03.047
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发表时间：
2010
影响因子：
2.5
通讯作者：
Lachman,HerbertM
中科院分区：
文献类型：
--
作者：
Shah,AbhishekK;Tioleco,NinaM;Nolan,Karen;Locker,Joseph;Groh,Katherine;Villa,Catalina;Stopkova,Pavla;Pedrosa,Erika;Lachman,HerbertM
在精神分裂症 (SZ) 患者亚组中发现了影响神经素 1 (NRXN1) 基因的拷贝数变异 (CNV)。 NRXN1 表达很复杂，由两个主要转录本产生多种选择性剪接形式； NRXN1α 和 NRXN1β。 SZ 中的大多数 CNV 都是影响近端 NRXN1α 外显子和启动子区域的缺失。罕见的染色体事件有助于理解复杂精神疾病的遗传基础，因为受影响的基因成为分析更微妙的遗传改变的可行目标。作为实现这一目标的第一步，我们对 170 名 SZ 患者和类似数量的对照者的 NRXN1α 启动子区域进行了重新测序。在患者群体中发现了两种罕见的突变。在对照中发现了一种以前未知的单核苷酸多态性 (SNP)。生物信息学分析表明，与几种转录因子的结合可能受到次要等位基因的影响。研究结果表明，除了破坏 NRXN1α 启动子的染色体改变外，该区域的罕见点突变也可能与 SZ 发病机制有关。
Copy number variants (CNVs) affecting the neurexin 1 (NRXN1) gene have been found in a subgroup of patients with schizophrenia (SZ). NRXN1 expression is complex, with multiple alternative splice forms generated from two major transcripts; NRXN1α and NRXN1β. The majority of CNVs in SZ are deletions affecting the proximal NRXN1α exons and promoter region. Rare chromosomal events are useful in understanding the genetic basis of complex psychiatric disorders since affected genes become feasible targets to analyze for more subtle genetic alterations. As a first step towards this goal, we resequenced the NRXN1α promoter region in 170 patients with SZ and a similar number of controls. Two rare mutations were identified in the patient population. One previously unknown single nucleotide polymorphism (SNP) was found in controls. Bioinformatics analysis suggests that binding to several transcription factors may be affected by the minor alleles. The findings suggest that in addition to chromosomal alterations disrupting the NRXN1α promoter, rare point mutations in the region may also be involved in SZ pathogenesis.