開啟異常基因 可望治療自閉症

pengxc

哈佛大學研究人員發現，許多自閉案例是由阻斷大腦學習的基因缺陷所造成，許多自閉症兒童在一歲前的大腦發育異常，與六個新基因有關。這項發現被視為具有開創性意義，因為部分基因並非喪失或損壞，而只是被ＤＮＡ控制區的突變所「關閉」。

前述發現為治療自閉症的可能性燃起希望，因為這些重要基因或許可透過藥物或行為與教育療程加以「開啟」，讓自閉症兒童的大腦得以正常發育。參與研究的遺傳專家摩洛說：「這意味如果我們了解如何活化這些基因，也許以藥物啟動它們，我們就不需加以取代。」

這項發表在「科學」期刊的研究強化了對自閉症的一般認定，亦即自閉症有其遺傳上、環境上的因素，同時也有助於解釋，為何密集的教育計畫對某些自閉兒有益：因為某些對經驗有反應的基因並未失去，只是卡在「關閉」狀態。自閉症行為治療的知名專家高斯坦醫師說：「迴路就在那兒，不過你必須額外推它一把。」

不過，該研究也顯示，自閉症過於個人化，每位病患皆有多樣的基因缺陷，因此難以發展出簡易的自閉症基因檢驗法。領導這項研究的哈佛醫學院首席基因學家威爾許說：「幾乎每個自閉兒都有其特別肇因。」

他表示，在美國，遺傳引起的自閉症佔該疾病總數僅約十五％，為此，他另闢研究蹊徑，轉向近親通婚風氣較盛的中東。研究團隊研究美國、約旦、沙烏地阿拉伯、科威特、安曼、巴基斯坦、卡達與土耳其等一百零四個有自閉兒的家庭，其中有八十八個家庭屬表、堂近親通婚。

近親通婚使得隱性突變，也就是帶有缺陷基因的健康雙親，孕育出不健康子嗣的發生率更普遍，研究人員說，表堂近親間的婚姻，增加天生神經畸形的機率約達百分之百。

Edmama

That's what I've just heard from one of the parents, and I'm still looking for this news on the Internet. If that is the case, we all will have hope and that even explians why "early intervention" is important. Thanks for sharing, and if you can provide the original link, that would be great!

pengxc

[face=Arial]Gene discoveries yield autism clues[/face]
Story Highlights Study: Genes suggest autism happens in brains that can't form proper connections

Some genes may have been stuck in "off" position, respond to therapy

Study reveals wide variety, almost a custom set, of gene defects in each patient

Genetic cause is known for only about 15 percent of autism cases

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WASHINGTON (AP) -- Harvard researchers have discovered half a dozen new genes involved in autism that suggest the disorder strikes in a brain that can't properly form new connections.

The findings also may help explain why intense education programs do help some autistic children -- because certain genes that respond to experience weren't missing, they were just stuck in the "off" position.

"The circuits are there but you have to give it an extra push," said Dr. Gary Goldstein of the Kennedy Krieger Institute in Baltimore, Maryland, which wasn't involved in the gene hunt but is well-known for its autism behavioral therapy.

The genetics suggest that "what we're doing makes sense when we work with these little kids -- and work and work and work -- and suddenly get through," he said.

But the study's bigger message is that autism is too strikingly individual to envision an easy gene test for it. Instead, patients are turning out to have a wide variety, almost a custom set, of gene defects.

"Almost every kid with autism has their own particular cause of it," said Dr. Christopher Walsh, chief of genetics at Children's Hospital Boston, Massachusetts, who led the research published in Friday's edition of the journal Science.

Autism spectrum disorders include a range of poorly understood brain conditions, from the mild Asperger's syndrome to more severe autism characterized by poor social interaction, impaired communication and repetitious behaviors.

It's clear that genes play a big role in autism, from studies of twins and families with multiple affected children. But so far, the genetic cause is known for only about 15 percent of autism cases, Walsh said.

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So Walsh's team took a new tack. They turned to the Middle East, a part of the world with large families and a tendency for cousins to marry, characteristics that increase the odds of finding rare genes. They recruited 88 families with cousin marriages and a high incidence of autism, from Jordan, Saudi Arabia, Kuwait, Oman, Pakistan, Qatar, Turkey and the United Arab Emirates. They compared the DNA of family members to search for what are called recessive mutations -- where mom and dad can be healthy carriers of a gene defect but a child who inherits that defect from both parents gets sick.

In some of the families, they found large chunks of missing DNA regions that followed that recessive rule. The missing regions varied among families, but they affected at least six genes that play a role in autism.

Here's why this matters: All the genes seem to be part of a network involved in a basic foundation of learning -- how neurons respond to new experiences by forming connections between each other, called synapses.

In the first year or two of life -- when autism symptoms appear _ synapses rapidly form and mature, and unnecessary ones are "pruned" back. In other words, a baby's brain is literally being shaped by its first experiences so that it is structurally able to perform learning and other functions of later life.

"This paper points to problems specifically in the way that experience sculpts the developing brain," explained Dr. Thomas Insel, director of the National Institute of Mental Health, which helped fund the work.

Some earlier research had pointed to the same underlying problem, so these newly found genes "join a growing list to suggest that autism is a synaptic disorder," he said.

If that sounds discouraging, here's the good news: The missing DNA didn't always translate into missing genes. Instead what usually was missing were the on/off switches for these autism-related genes. Essentially, some genes were asleep instead of doing their synapse work.

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"I find that hopeful" because "there are ways that are being discovered to activate genes," Walsh said. "This might be an unanticipated way of developing therapies in the long term for autism: Identifying these kids where all the right genes are present, just not turned on in the right way."

At Kennedy Krieger, Goldstein thinks the work may provide a gene-level explanation for why some children already are helped by intense therapy.

"We have trouble getting through to these children, but with repeated stimulation we can do it," he said. "These are circuits that have an ability not so much to recover but to work around the problem."

清晨一片寂静

英语看不懂

blackeye

pengxc: 我把这篇文章推荐到‘译言’去了，但愿有人能把它翻过来，让更多的人了解。

http://www.yeeyan.com/articles/source/51354_097/Gene_discoveries_yield_autism_clues

我在译言还建了一个小组叫‘孤独症’，专门收集有关孤独症的翻译文章。可是目前全译言里只有六篇。我知道做星妈星爸都很辛苦。不过有哪位喜欢将鸟文转换成方块字的，欢迎加入‘孤独症’小组，忙里偷闲翻译几篇。小组链接如下：

http://www.yeeyan.com/groups/show/Autism

vincent

得空把主要的内容翻译了一下，先凑合着看。

哈佛研究者已经发现几个与孤独症有关的基因，从而推测这种症状是因为大脑不能建立合适的新的连接。

这个发现也许可以解释为什么强化训练能够帮助一些孤独症的孩子 – 因为某些响应经历的基因处于‘关闭’状态，而我们常人却没有这个问题。

马里兰巴尔第莫的肯尼迪。克里格学院格德斯坦医生是有名的孤独症行为治疗专家，虽然他没有参与搜寻缺陷基因的研究，但指出: ‘(基因的)连接是存在的，但需要一个确切的驱动。’

他说：‘遗传学的研究表明我们在这些孩子身上做的工作是有意义的，不断不断地训练，然后突然间他们就好了。’

麻省的波士顿儿童医院遗传学主任克里斯多夫。沃尔士医生领导了这项研究，并且把结果发表于星期五的《科学》杂志上。他说：‘几乎每个孤独症孩子都有各自不同的原因。’

孤独症障碍谱系包括中度的亚士伯格症到严重的孤独症，特征为社会交往能力差、沟通能力缺陷和刻板行为，这些都和大脑行为有关，但我们知之甚少。

对于双胞胎和多重患儿家庭的研究表明，基因在孤独症中起很大的作用。但是根据沃尔士医生的说法，目前为止只有15%的孤独症可以归结为遗传的原因。

学习机制是神经系统怎样响应新的经历从而形成连接的过程，也就是所谓的synapse，而那些（与孤独症有关的）基因似乎正是这个网络中的一部分。

在出生后的第一、二年，也就是孤独症刚形成时，synapse快速形成并成熟。也就是说，一个婴儿的大脑被最初始经历塑造，使得它结构上在以后的生活中去完成学习和其它功能。

国家精神卫生机构赞助了这项研究。该机构的托马斯。英塞尔博士说：‘这个研究特别揭示了经历塑造大脑发展的问题。’他进一步说：‘早期已有一些研究指出了同样的问题，因此这些新发现的基因为孤独症是synaptic障碍提供了新的证据。’

人们不必为此项研究结果而失落。因为丢失的并不是一些基因，而是这些与孤独症有关的基因丢失了开-关的功能。基本上讲，这些基因失活了，从而不能完成synapse的功能。

沃尔士说：‘我发现这很有希望。因为有些方法被发现能激活这些基因。长期训练可能就起到这样的作用。这些孩子所有的基因都不缺，但却没有被正确启动，我们就是要帮助他们。’

肯尼迪。克里格学院格德斯坦很感激这项研究从基因角度解释了为什么很多孩子从高强度训练中得到了帮助。他说；‘我们在治愈这些孩子方面有大问题，但通过不断刺激，我们最起码可以解决一些问题，虽然还不能完全解决。’

LittleKoala

下面引用由vincent发表的内容：
人们不必为此项研究结果而失落。因为丢失的并不是一些基因，而是这些与孤独症有关的基因丢失了开-关的功能。基本上讲，这些基因失活了，从而不能完成synapse的功能。

沃尔士说：‘我发现这很有希望。因为有些方法被发现能激活这些基因。长期训练可能就起到这样的作用。这些孩子所有的基因都不缺，但却没有被正确启动，我们就是要帮助他们。’

多谢vincent，这是读过的最令人振奋的消息了。

sxy

好想变做一个小锤，把这些丢失功能的基因逐个敲开。
感谢V大哥百忙之中的翻译，您辛苦了。

niuniuma

“里格学院格德斯坦很感激这项研究从基因角度解释了为什么很多孩子从高强度训练中得到了帮助。他说；‘我们在治愈这些孩子方面有大问题，但通过不断刺激，我们最起码可以解决一些问题，虽然还不能完全解决”.

还看到过一种比喻说法，就是主路被关闭了，但是旁枝末道还开着。所以要通过高强度的训练，把旁枝末到打通扩大，起到主道的作用。

我自己想出的比喻，有点像成年人学外语吧，主要的语言神经通道都关了，但是还可以从语言的支路通道学新的语言，可是，永远也学不好，说话速度慢，听力理解慢，词汇量不够，感情丰富但表达不出来，听别人讲隐喻典故听不懂。也就刚能应付简单的生活。

LittleKoala

下面引用由niuniuma发表的内容：
我自己想出的比喻，有点像成年人学外语吧，主要的语言神经通道都关了，但是还可以从语言的支路通道学新的语言，可是，永远也学不好，说话速度慢，听力理解慢，词汇量不够，感情丰富但表达不出来，听别人讲隐喻典故听不懂。也就刚能应付简单的生活。

谢谢niuniuma的比喻，感同身受，不过儿子能达到这个地步就很高兴了。

vincent

我review了一下，发现这句‘（基因的)连接是存在的，但需要一个确切的驱动。’ 应该为‘额外的驱动’。我把extra看成exact了。

谢谢考拉妈和信义妈的ABA强化物。

pengxc

谢谢翻译。synapse的中文意思是“神经突触”。你还可以通过“修改”功能把译文重新完善。