Ishizuka Kanako, Kimura Hiroki, Yoshimi Akira, Banno Masahiro, Kushima Itaru, Uno Yota, Okada Takashi, Mori Daisuke, Aleksic Branko, Ozaki Norio
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Nagoya J Med Sci. 2016 Dec;78(4):465-474. doi: 10.18999/nagjms.78.4.465.
(Methyl-CpG-binding domain 5) is a critical gene for normal development. While deletion or duplication of may contribute to a genetic predisposition to autism spectrum disorders (ASD), intellectual disability, or epilepsy, the impact of rare single nucleotide variants (SNVs) on neurodevelopmental features, particularly features with late onset, has not been fully explored. In this study, we conducted exon-targeted resequencing of with next-generation sequencing technology in 562 Japanese patients (192 with idiopathic ASD and 370 with schizophrenia (SCZ)) and detected 16 SNVs with allele frequencies of ≤1%. We then performed phenotype analyses with 12 novel variants of these 16 SNVs. SCZ patients with these variants exhibited mainly within normal development ranges until the first psychosis and ASD patients with SNVs did not precisely overlap with the core characteristics described in previous literature as being associated with SNVs. Our results suggested that variants might contribute to a broad spectrum of neurodevelopmental pathophysiology. Further research and assessment of clinical diagnostic screening are necessary for understanding the burden of rare SNVs for these neurodevelopmental disorders.
（甲基化CpG结合结构域5）是正常发育的关键基因。虽然其缺失或重复可能导致自闭症谱系障碍（ASD）、智力残疾或癫痫的遗传易感性，但罕见单核苷酸变异（SNV）对神经发育特征的影响，尤其是对迟发性特征的影响，尚未得到充分研究。在本研究中，我们利用下一代测序技术对562名日本患者（192名特发性ASD患者和370名精神分裂症（SCZ）患者）进行了该基因的外显子靶向重测序，并检测到16个等位基因频率≤1%的SNV。然后，我们对这16个SNV中的12个新变异进行了表型分析。携带这些变异的SCZ患者在首次出现精神病之前主要表现为发育正常，而携带SNV的ASD患者与先前文献中描述的与该基因SNV相关的核心特征并不完全重叠。我们的结果表明，该基因变异可能导致广泛的神经发育病理生理学。为了了解这些罕见的该基因SNV对这些神经发育障碍的影响，有必要进行进一步的研究和临床诊断筛查评估。
