来源：生物谷
近日，美国研究人员宣称，与大脑功能建立连接的一种基因可能对于形成自闭症具有重要意义。
一种叫做“contactin 4”基因的瓦解损失将停止其正常工作，并使大脑正常的工作网络中断。这项研究报告发表在《医学遗传学期刊》（Journal of Medical Genetics）上。负责此项研究的纽约州立大学石溪分校伊莱·哈奇韦尔博士称，儿童体内出现三组contactin 4基因瓦解或者三组中有一组瓦解，均将导致2.5%患自闭症的几率。
哈奇韦尔在一次电话采访中说，“通常人们都错误地认为自闭症是由于后天因素导致的，并没有想到这种病症会与遗传基因突变有联系。”他表示将这项研究 添加到了自闭症潜在测试列表之中，或许将有助于对泛自闭症的治疗。泛自闭症是一种会影响儿童多方面功能的发育障碍，此障碍特征是沟通技巧迟缓、社交互动和 思维想像能力出现障碍。
哈奇韦尔的研究小组对来自81个家庭的92位泛自闭症患者与560位无自闭症人群进行对比，他们做出一个完整的基因组分 析，观看完整的DNA图，结果发现其中有三位患者的contactin 4基因不完整，其DNA片断出现瓦解受损。这些患者都是从未患自闭症的父亲那里继承该基因，患者表现出严重的社交障碍、发育延迟，甚至出现智力迟缓。他强 调称，许多人认为自闭症患者人群是一个小数目，实际上全球有数百万自闭症患者。美国疾病控制和预防中心评估每150个儿童中就有1个自闭症患者，或者是相 关的亚斯柏格症患者（该病症经常表现为轻微的社交笨拙）。
Contactin 4基因是一个发育状态中的轴突，轴突一般是传导远离神经元的神经纤维突，它们可以形成一个长线排列，彼此神经元之间进行连接。哈奇韦尔指出，这种基因突变 是出现于婴儿出生时。一些病例中，儿童患者有自闭症而其父亲却是正常的，但实际上自闭症始终与基因有直接关系，时常有一些病例显示自己是正常的，但是他们 的后代却患有严重自闭症。这可能是父亲在儿童时期曾有轻微的亚斯柏格症或相应的某些症状，但他却未曾进行诊断。目前，美国许多成年人在他儿童时期很少去医 院就诊检查是否患有自闭症，而他们的父辈接受诊断的几率则更低。
这是一个富有争议的话题，一些专家称自闭症和相关的疾病患者是近年内人数骤增，而另一些专家表示目前没有证据足以证实以上结论。哈奇韦尔说，“我个 人观点认为自闭症并不是近年来才变得很普遍，现今如果家长意识到孩子在学习方面存在问题，便会尽可能地诊断为自闭症患者，以寻找学校多方面的教育帮助。”
据了解，哈奇韦尔帮助建立了人群诊断生物科技公司，以开展症状前DNA分析和早期侦查探测自闭症、阿茨海默症、帕金森氏症、糖尿病和其他遗传疾病。（生物谷Bioon.com）
生物谷推荐原始出处：
Journal of Medical Genetics 2009;46:176-182
Disruption of contactin 4 in three subjects with autism spectrum disorder
J Roohi1, C Montagna2, D H Tegay3,4, L E Palmer5, C DeVincent3, J C Pomeroy3, S L Christian6, N Nowak7 and E Hatchwell1,8
1 Department of Genetics, Stony Brook University, Stony Brook, New York, USA
2 Department of Pathology and Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York, USA
3 Department of Pediatrics, Stony Brook University Medical Center, Stony Brook, New York, USA
4 Department of Medicine & Medical Genetics, New York College of Osteopathic Medicine, Old Westbury, New York, USA
5 Department of Microbiology, Stony Brook University, Stony Brook, New York, USA
6 Department of Human Genetics, The University of Chicago, Chicago, Illinois, USA
7 Department of Cancer Prevention and Population Sciences, RPCI and New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, New York, USA
8 Department of Pathology, Stony Brook University, Stony Brook, New York, USA
Correspondence to:
Dr E Hatchwell, Department of Pathology, BST-9, SUNY at Stony Brook, Stony Brook, NY 11794-8691, USA;
ABSTRACT
Background: Autism spectrum disorder (ASD) is a developmental disorder of the central nervous system of largely unknown aetiology. The prevalence of the syndrome underscores the need for biological markers and a clearer understanding of pathogenesis. For these reasons, a genetic study of idiopathic ASD was undertaken.
Methods and results: Array based comparative genomic hybridisation identified a paternally inherited chromosome 3 copy number variation (CNV) in three subjects: a deletion in two siblings and a duplication in a third, unrelated individual. These variations were fluorescence in situ hybridisation (FISH) validated and the end points further delineated using a custom fine tiling oligonucleotide array. Polymerase chain reaction (PCR) products unique to the rearrangements were amplified and sequence analysis revealed the variations to have resulted from Alu Y mediated unequal recombinations interrupting contactin 4 (CNTN4).
Conclusion: CNTN4 plays an essential role in the formation, maintenance, and plasticity of neuronal networks. Disruption of this gene is known to cause developmental delay and mental retardation. This report suggests that mutations affecting CNTN4 function may be relevant to ASD pathogenesis.
