A part of patients with autism spectrum disorder has haploidy of HPC-1/syntaxin1A gene that possibly causes behavioral disturbance as in experimentally gene ablated mice
A part of patients with autism spectrum disorder has haploidy of HPC-1/syntaxin1A gene that possibly causes behavioral disturbance as in experimentally gene ablated mice
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DOI：
10.1016/j.neulet.2017.02.052
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发表时间：
2017-03-22
影响因子：
2.5
通讯作者：
Akagawa, Kimio
中科院分区：
文献类型：
--
作者：
Kofuji, Takefumi;Hayashi, Yuko;Akagawa, Kimio
自闭症谱系障碍（ASD）是高度遗传的，包括各种神经精神障碍，表现广泛。HPC-1异紫杉醇1A（STX 1A）编码调节神经递质和神经调质分泌的神经元质膜蛋白。STX 1A基因消融小鼠（无效和杂合子突变体）表现出异常的行为特征类似于人类自闭症症状，伴随着单胺分泌减少。为了确定STX 1A基因拷贝数的变化及其表达的变化是否与ASD相关，如在STX 1A基因消融小鼠中，我们对ASD患者的血液或唾液样本进行了拷贝数测定和实时定量RT-PCR。我们发现，一些ASD患者是STX 1A基因的单倍体，类似于STX 1A杂合子突变小鼠。而STX 1A基因单倍性ASD患者的父母和同胞STX 1A基因拷贝数均正常。在基因单倍性的ASD患者中，STX 1A mRNA表达降低至其父母的一半左右。因此，部分ASD患者存在STX 1A基因单倍性，STX 1A基因表达降低。(C)2017爱思唯尔B. V.保留所有权利。
Autism spectrum disorder (ASD) is highly heritable and encompasses a various set of neuropsychiatric disorders with a wide-ranging presentation. HPC-1 isyntaxinlA (STX1A) encodes a neuronal plasma membrane protein that regulates the secretion of neurotransmitters and neuromodulators. STX1A gene ablated mice (null and heterozygote mutant) exhibit abnormal behavioral profiles similar to human autistic symptoms, accompanied by reduction of monoamine secretion. To determine whether copy number variation of STX1A gene and the change of its expression correlate with ASD as in STX1A gene ablated mice, we performed copy number assay and real-time quantitative RT-PCR using blood or saliva samples from ASD patients. We found that some ASD patients were haploid for the STX1A gene similar to STX1A heterozygote mutant mice. However, copy number of STX1A gene was normal in the parents and siblings of ASD patients with STX1A gene haploidy. In ASD patients with gene haploidy, STX1A mRNA expression was reduced to about half of their parents. Thus, a part of ASD patients had haploidy of STX1A gene and lower STX1A gene expression. (C) 2017 Elsevier B.V. All rights reserved.