Association between microdeletion and microduplication at 16p11.2 and autism
Association between microdeletion and microduplication at 16p11.2 and autism
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DOI：
10.1056/nejmoa075974
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发表时间：
2008-02-14
影响因子：
158.5
通讯作者：
Daly, Mark J.
中科院分区：
文献类型：
--
作者：
Weiss, Lauren A.;Shen, Yiping;Daly, Mark J.
背景：自闭症谱系障碍是一种可遗传的发育障碍，认为染色体异常被认为起作用。搜索来自自闭症的751个多重家族的基因型数据中的副本数量变化。在波士顿儿童医院和冰岛的大型人群研究中，进一步评估了从头事件的特定复发事件。退分：在协议家庭中，我们观察到五个从16p11.211.211.211.211.211.211.211.211.211.211.211.211.21.211.21.211.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.21.2 kb。 。使用比较基因组杂交，我们观察到512名儿童中有5名与波士顿儿童医院的512名儿童有关发育延迟，智力低下或怀疑自闭症谱系障碍以及299名冰岛人群自闭症患者中的3例相同的缺失；删除还由18,834个未经冰岛控制的受试者中的2个携带。该地区的相互重复发生在约定家庭中的7名受影响的人中，波士顿儿童医院的512名儿童中有4个发生。复制似乎也是一个高渗透率的风险因素。判断：我们已经确定了一种新颖的，经常性的微骨骼和相互的微杀解性，具有很大的自闭症敏感性，并且似乎占病例的大约1％。我们没有识别出具有类似从头突变的类似聚集的其他区域。 `
Background: Autism spectrum disorder is a heritable developmental disorder in which chromosomal abnormalities are thought to play a role.Methods: As a first component of a genomewide association study of families from the Autism Genetic Resource Exchange (AGRE), we used two novel algorithms to search for recurrent copy-number variations in genotype data from 751 multiplex families with autism. Specific recurrent de novo events were further evaluated in clinical-testing data from Children's Hospital Boston and in a large population study in Iceland.Results: Among the AGRE families, we observed five instances of a de novo deletion of 593 kb on chromosome 16p11.2. Using comparative genomic hybridization, we observed the identical deletion in 5 of 512 children referred to Children's Hospital Boston for developmental delay, mental retardation, or suspected autism spectrum disorder, as well as in 3 of 299 persons with autism in an Icelandic population; the deletion was also carried by 2 of 18,834 unscreened Icelandic control subjects. The reciprocal duplication of this region occurred in 7 affected persons in AGRE families and 4 of the 512 children from Children's Hospital Boston. The duplication also appeared to be a high-penetrance risk factor.Conclusions: We have identified a novel, recurrent microdeletion and a reciprocal microduplication that carry substantial susceptibility to autism and appear to account for approximately 1% of cases. We did not identify other regions with similar aggregations of large de novo mutations. `