Identification of rare variants in KCTD13 at the schizophrenia risk locus 16p11.2.
Identification of rare variants in KCTD13 at the schizophrenia risk locus 16p11.2.
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DOI：
10.1097/ypg.0000000000000145
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发表时间：
2016-12
影响因子：
0.9
通讯作者：
Nöthen MM
中科院分区：
文献类型：
--
作者：
Degenhardt F;Heinemann B;Strohmaier J;Pfohl MA;Giegling I;Hofmann A;Ludwig KU;Witt SH;Ludwig M;Forstner AJ;Albus M;Schwab SG;Borrmann-Hassenbach M;Lennertz L;Wagner M;Hoffmann P;Rujescu D;Maier W;Cichon S;Rietschel M;Nöthen MM
16p11.2重复是精神分裂症（SCZ）的危险因素。使用转基因斑马鱼，Golzio及其同事将16p11.2内的KCTD 13确定为在人类中观察到的神经精神表型的主要驱动因素。本研究的目的是探讨KCTD 13在SCZ的发展中的作用，并提供一个更完整的图片在这个风险位点的等位基因结构。对576例患者进行KCTD 13基因外显子测序。突变c.6G> T和c.598G> A分别在一名患者中鉴定。这两种突变被预测为功能相关的，并且在1000个基因组计划数据和外显子组变体服务器中不存在。预测突变c.6G> T消除特异性蛋白1的潜在转录因子结合位点。与对照组相比，SCZ患者的特异性蛋白1表达发生了改变。需要在大型队列中进行进一步研究，以确定这两种已鉴定突变的相关性。
Duplications in 16p11.2 are a risk factor for schizophrenia (SCZ). Using genetically modified zebrafish, Golzio and colleagues identified KCTD13 within 16p11.2 as a major driver of the neuropsychiatric phenotype observed in humans. The aims of the present study were to explore the role of KCTD13 in the development of SCZ and to provide a more complete picture of the allelic architecture at this risk locus. The exons of KCTD13 were sequenced in 576 patients. The mutations c.6G>T and c.598G>A were identified in one patient each. Both mutations were predicted to be functionally relevant and were absent from the 1000 Genomes Project data and the Exome Variant Server. The mutation c.6G>T was predicted to abolish a potential transcription factor-binding site for specifity protein 1. Altered specifity protein 1 expression has been reported in SCZ patients compared with controls. Further studies in large cohorts are warranted to determine the relevance of the two identified mutations.