Ambalavanan Amirthagowri, Girard Simon L, Ahn Kwangmi, Zhou Sirui, Dionne-Laporte Alexandre, Spiegelman Dan, Bourassa Cynthia V, Gauthier Julie, Hamdan Fadi F, Xiong Lan, Dion Patrick A, Joober Ridha, Rapoport Judith, Rouleau Guy A
Department of Human Genetics, McGill University, Montreal, QC, Canada.
Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD, USA.
Eur J Hum Genet. 2016 Jun;24(6):944-8. doi: 10.1038/ejhg.2015.218. Epub 2015 Oct 28.
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.
儿童期起病的精神分裂症（COS）定义为在13岁之前发病，是一种病因不明的罕见严重神经发育障碍。最近，测序研究在成人起病的精神分裂症和自闭症散发病例中发现了罕见的、可能致病的新生变异。在本研究中，我们对17个COS三联体进行了外显子组测序，以测试新生变异是否可能导致这种疾病。我们在17名COS先证者中鉴定出20个新生变异，这与该疾病成人形式中报道的新生突变率一致。有趣的是，COS中的错义新生变异具有很高的致病性可能性，并且富含对变异耐受性较低的基因。在我们的研究中发现被破坏的基因中，SEZ6、RYR2、GPR153、GTF2IRD1、TTBK1和ITGA6之前已与神经元功能或精神障碍相关联，因此可被视为COS候选基因。
