De novo variants in sporadic cases of childhood onset schizophrenia.
De novo variants in sporadic cases of childhood onset schizophrenia.
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DOI：
10.1038/ejhg.2015.218
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Rouleau GA
中科院分区：
文献类型：
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作者：
Ambalavanan A;Girard SL;Ahn K;Zhou S;Dionne-Laporte A;Spiegelman D;Bourassa CV;Gauthier J;Hamdan FF;Xiong L;Dion PA;Joober R;Rapoport J;Rouleau GA
儿童期发病的精神分裂症 (COS) 是指 13 岁之前发病，是一种罕见的、病因不明的严重神经发育障碍。最近，测序研究在成人发病的精神分裂症和自闭症散发病例中发现了罕见的、可能致病的新发变异。在这项研究中，我们对 17 个 COS 三人组进行了外显子组测序，以测试新生变异是否会导致这种疾病。我们在 17 名 COS 先证者中鉴定出 20 个新发变异，这与该疾病成人形式报告的新发突变率一致。有趣的是，COS 中的错义从头变异体具有很高的致病性，并且富集了对变异体耐受性较差的基因。在我们的研究中发现被破坏的基因中，SEZ6、RYR2、GPR153、GTF2IRD1、TTBK1 和 ITGA6 先前已被认为与神经元功能或精神疾病有关，因此可能被视为 COS 候选基因。
Childhood-onset schizophrenia (COS), defined by the onset of illness before age 13 years, is a rare severe neurodevelopmental disorder of unknown etiology. Recently, sequencing studies have identified rare, potentially causative de novo variants in sporadic cases of adult-onset schizophrenia and autism. In this study, we performed exome sequencing of 17 COS trios in order to test whether de novo variants could contribute to this disease. We identified 20 de novo variants in 17 COS probands, which is consistent with the de novo mutation rate reported in the adult form of the disease. Interestingly, the missense de novo variants in COS have a high likelihood for pathogenicity and were enriched for genes that are less tolerant to variants. Among the genes found disrupted in our study, SEZ6, RYR2, GPR153, GTF2IRD1, TTBK1 and ITGA6 have been previously linked to neuronal function or to psychiatric disorders, and thus may be considered as COS candidate genes.