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【资讯翻译】Genetic Deletion May Explain Language Delays in Autism, Oth...

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发表于 2015-2-27 15:24:32 | 显示全部楼层 |阅读模式

Genetic Deletion May Explain Language Delays in Autism, Other Disorders

Children with a genetic deletion previously linked to autism and other neurodevelopmental disorders have measurable delays in processing sound and language, a new study suggests.

An imaging study conducted by investigators at the Children's Hospital of Philadelphia (CHOP), in Pennsylvania, showed that a deletion of a region on chromosome 16 (16p11.2) was linked to a "stunningly high" auditory processing delay known as the M100 response latency.

"This study shows an important connection between gene differences and differences in neurophysiology," study lead investigator Timothy Roberts, PhD, at CHOP's Center for Autism Research, said in a statement. "It may also help to bridge a largely unexplored gap between genetics and behavior."

The study was published online February 11 in the journal Cerebral Cortex.

Genetics First Approach

Previous research has shown that copy number variants, either deletions or duplications, at the 16p11.2 location on chromosome 16 are associated with neurodevelopmental problems, including autism spectrum disorder (ASD), language impairment, and developmental delays.

Dr Roberts and colleagues used magnetoencephalography (MEG) to measure auditory processing in 115 children: 43 with 16p11.2 deletion, including 11 with ASD; 23 with 16p11.2 duplication, including two with ASD; and 49 age-matched children who served as control participants.

The primary indicator of auditory processing impairment was the latency of the M100 auditory response detected by MEG.

Compared with control children, children with 16p11.2 deletion had a significant 23-ms delay in auditory processing, which is "stunningly high," Dr Roberts said in a statement. A delay was not seen in children with 16p11.2 duplication. On the contrary, these children had a tendency to process sounds faster than the control children.

The 23-ms delay, about one fortieth of a second, is twice as high as the 11-ms M100 delay that Dr Roberts and colleagues found in a 2010 MEG study of children with ASD published in Autism Research.

An 11-ms delay means that a child hearing the word "elephant" would still be processing the "el" sound while other children moved on, with delays cascading as a conversation progresses, said Dr Roberts.

Although the 2010 study focused on children with ASD, the current study took a "genetics first" approach, studying children known to have genetic variants with or without ASD.

This study points to a "genetic basis for a delayed M100," he told Medscape Medical News. "There may, of course, be other genetic factors in other patients who would also have an M100. This elevates our previous findings of delayed M100 in ASD from 'observational' towards 'biologically-interpretable.' "

"Specifically, it suggests that some genes in the 16p11.2 region may have a role in the biological pathway necessary for an efficient (on-time) neural response. It is, of course, very important for sensation, perception, and cognition that neural signals propagate efficiently through the brain, (because) delays cascade to impairments," he noted.

Dr Roberts said a better understanding of the pathways controlled by the genes in this region may help in identifying targets for drug development. This research might also help in identifying a "biologically relevant biomarker for enriching/monitoring clinical trials."

Dr Roberts said his laboratory is planning a small pilot study of children with ASD who have M100 response latency to see whether a drug that acts on synaptic transmissions can reduce M100 auditory delays.

Interpret Cautiously

Reached for comment, Renee Lajiness-O'Neill, PhD, from Eastern Michigan University, in Ypsilanti, said it is "an alluring study that attempts to link an atypical neurophysiological response to a genetic underpinning."

A number of researchers have suggested that aberrant development of fundamental auditory sensory cortices revealed through, for example, a delay in the basic M100 auditory evoked response contributes to a subsequent cascading disruption of higher-level language development.

This new study suggests a "clear link between those children with a 16p11.2 deletion and an ~20 ms delay of the M100 auditory evoked response, and this doesn't appear to be accounted for by other factors, such as gender, intellectual abilities. This suggests that genes within this ~600-kb deletion appear essential for this vital M100 auditory evoked response," Dr Lajiness-O'Neill added.

However, any link to language delays in children with ASD "should be interpreted with caution," she said, because of the small numbers of children who met diagnostic criteria for ASD.

"It will be important to examine this effect in a larger cohort of children with comorbid 16pq11.2 and ASD. It is certainly plausible that a study with a larger 16pq11.2/ASD cohort could yield a unique language-impaired risk profile for an ASD subtype that is distinct from idiopathic ASD," Dr Lajiness-O'Neill said. "As such, novel interventions for this discrete language-impaired profile might be developed as we drilled further into the unique pathophysiological contributions."

信源地址:http://www.medscape.com/viewarticle/840456

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发表于 2015-2-27 16:52:18 | 显示全部楼层
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发表于 2015-3-3 15:21:20 | 显示全部楼层
Genetic Deletion May Explain Language Delays in Autism, Other Disorders
基因缺失或可解释自闭症和其它疾病儿童的语言延迟

    一项新的研究表明,有一个基因缺失(早先认为与自闭症以及神经发育疾病相关)的儿童有明显的声音和语言处理延迟。
    来自宾夕法尼亚轴费城儿童医院(CHOP)的研究人员开展了一项影像研究,结果显示16号染色体(16p11.2)某个区域缺失与高度听觉处理延迟(称为M100反应潜伏期)相关。
    “这项研究显示基因差异和神经生理差异之间有重要联系。”该研究首席科学家Timothy Roberts(PhD,CHOP自闭症研究中心)声明称,“它也可能帮助在遗传学和行为学之间尚未研究清楚的地方建立联系的桥梁。”
    该研究发表在2月11号的《大脑皮层杂志》(Cerebral Cortex)上。
    遗传优先方式
    早先的研究显示16号染色体16p11.2位置拷贝数差异(无论是缺失或重复)与包括自闭症(ASD)、语言障碍以及发育延迟等神经发育问题有关。
    Roberts博士及其同事运用脑磁描记法在115名儿童中测试听觉处理。这些儿童中有43名是16p11.2缺失(11名患有ASD),23名是16p11.2重复(2名患有ASD)。其余49名年纪相仿的儿童作为对照参与研究。
    听觉处理障碍的主要指标为通过MEG检测的M100听觉反应潜伏期。
    与对照儿童相比,16p11.2缺失儿童在听觉处理上有明显的23毫秒延迟,这是相当令人惊异的,Roberts博士声明。而16p11.2重复的儿童则没有延迟的现象,相反这些儿童处理声音的速度比对照儿童要块。
    23毫秒,约等于1/40秒的延迟,是Roberts博士及其同事在2010年ASD儿童的MEG研究【发表在《自闭症研究》(Autism Research)】中发现的11毫秒M100延迟的两倍。
    11毫秒的延迟意味着当正常儿童已经处理完“elephant”这个单词时,延迟儿童还刚处理到“el”,也就是说在谈话时大量落下单词,Roberts博士如是说。
    尽管2010年的研究主要集中在ASD儿童上,而现在的研究采用遗传优先的方式来研究遗传差异儿童(无论是否患有ASD)。
    这项研究指向“M100延迟的遗传基础”,他对Medscape Medical News这样说道,“当然,其余那些有M100的患者可能有其他的遗传因素。这使我们将早先M100延迟的发现从观察到的转变为生物学上判断。”
    “具体而言,这意味着16p11.2区域的某些基因可能在高效(及时)的神经反应必需的生物通路中有重要作用。当然,这对于感觉、视觉感受以及认知这些需要通过大脑高效传递神经信号的知觉而言是非常重要的,因为延迟关联着障碍。”他强调。
    Roberts博士认为对这些由这个区域的基因控制的通路有更好的认识将有助于新药研发时鉴别作用靶点。这项研究可能有助于确定一个生物学上重要的生物标记,有助于充实并监控临床试验。
    Roberts博士称他的实验室计划对有M100反应潜伏期的ASD儿童患者开展一个小的初步研究来观察作用于突触传递的新药是否能降低M100听觉延迟。
    谨慎的解释
    Renee Lajiness-O'Neill(PhD,东密歇根大学)博士评论认为这是一项很吸引人的研究,它试图将非典型的神经生理学反应与遗传基础联系起来。
    许多研究人员认为基础听觉皮质的不正常发育揭示了通过例如基础M100听觉诱发反应的延迟促使随后高级语言发育的大量中断。
    这项新研究揭示了16p11.2缺失儿童与M100听觉诱发反应中大约20毫秒延迟之间清晰的联系,而这似乎也并不是由其它因素(诸如性别、智力)引起的。这说明这段大约600kb缺失区的基因似乎是这至关重要的M100听觉诱发反应所必需的,Renee Lajiness-O'Neill博士补充说。
    然而,任何关系到ASD儿童语言延迟的说法都需要谨慎解释,她说到,因为触及ASD诊断标准的儿童数量太少。
    “在一个更大的同时有16bp11.2和ASD的儿童群体中检查这种效果将是十分重要的。在一个更大的16pq11.2/ASD群体中进行的研究可以针对ASD亚型(区别于先天性ASD)进行语言系统障碍风险预测,这当然是有一定合理性的。” Renee Lajiness-O'Neill博士说,“既然如此,针对这种分散的语言系统障碍风险的新型干预方式可能会随着我们对这种独特的病理生理学贡献的深入研究而进步。”

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发表于 2015-3-30 09:18:43 | 显示全部楼层
这个栏目好,希望斑竹和大家一起翻译,对我们这些医学生来说非常有帮助
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