Copy number variations associated with autism spectrum disorders contribute to a spectrum of neurodevelopmental disorders
Copy number variations associated with autism spectrum disorders contribute to a spectrum of neurodevelopmental disorders
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DOI：
10.1097/gim.0b013e3181f0c5f3
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发表时间：
2010-11-01
影响因子：
8.8
通讯作者：
Shaffer, Lisa G.
中科院分区：
文献类型：
--
作者：
Rosenfeld, Jill A.;Ballif, Blake C.;Shaffer, Lisa G.
目的：自闭症谱系障碍是一系列神经发育障碍，已被证明具有很强的遗传病因成分。基于微阵列的比较基因组杂交和其他分子细胞遗传学技术正在发现自闭症谱系障碍患者中越来越多的拷贝数变异。方法：我们在实验室对自闭症谱系障碍患者进行了基于基因芯片的异常比较基因组杂交结果的检验。我们还检查了另外151名自闭症特征的存在，这些人被转介进行基于微阵列的比较基因组杂交测试，以寻找自闭症谱系障碍以外的指征，但基因组改变与自闭症谱系障碍病例中发现的重叠。结果：我们确定了1461名被推荐进行自闭症谱系障碍测试的个体，在使用全基因组阵列分析的个体中，大约11.6%的个体报告了可能存在显著异常的情况。这些异常包括包含新的候选基因的变化，如SNTG2、SOX5、HFE和TRIP38。少数有重叠异常的个体(19%)有自闭症特征，我们研究中发现的许多拷贝数变异是遗传的(在自闭症谱系障碍个体中发现的那些拷贝数变异的69%)。结论：我们的结果表明，这些拷贝数变异是导致自闭症谱系障碍表型发展的多种因素之一。此外，具有这些拷贝数变异的患者的广泛表型谱表明，这些拷贝数变异并不是自闭症谱系障碍特有的，而是更普遍地可能损害神经发育。Genet Med 2010：12(11)：694-702。
Purpose: Autism spectrum disorders represent a range of neurodevelopmental disorders that have been shown to have a strong genetic etiological component. Microarray-based comparative genomic hybridization and other molecular cytogenetic techniques are discovering an increasing number of copy number variations in individuals with autism spectrum disorder. Methods: We examined the yield of abnormal microarray-based comparative genomic hybridization findings in our laboratory for individuals referred for testing for autism spectrum disorder. We also examined the presence of autistic features among 151 additional individuals who were referred for microarray-based comparative genomic hybridization testing for indications other than autism spectrum disorder but had genomic alterations overlapping those found in cases referred for autism spectrum disorder. Results: We identified 1461 individuals referred for testing for autism spectrum disorder, with likely significant abnormalities reported in approximately 11.6% of individuals analyzed with whole-genome arrays. These abnormalities include alterations that encompass novel candidate genes such as SNTG2, SOX5, HFE, and TRIP38. A minority of individuals with overlapping abnormalities (19%) had autistic features, and many of the copy number variations identified in our study are inherited (69% among those found in individuals with autism spectrum disorder). Conclusions: Our results suggest these copy number variations are one of multiple factors contributing to the development of an autism spectrum disorder phenotype. Additionally, the broad phenotypic spectrum of the patients with these copy number variations suggests that these copy number variations are not autism spectrum disorder-specific but likely more generally impair neurodevelopment. Genet Med 2010:12(11):694-702.