The Number of Genomic Copies at the 16p11.2 Locus Modulates Language, Verbal Memory, and Inhibition
The Number of Genomic Copies at the 16p11.2 Locus Modulates Language, Verbal Memory, and Inhibition
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DOI：
10.1016/j.biopsych.2015.10.021
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发表时间：
2016-07-15
影响因子：
10.6
通讯作者：
Jacquemont, Sebastien
中科院分区：
文献类型：
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作者：
Hippolyte, Loyse;Maillard, Anne M.;Jacquemont, Sebastien
背景：16p11.2BP4-BP5基因座的缺失和重复是常见的拷贝数变异，与自闭症谱系障碍和精神分裂症高度相关。除了语言和全球认知之外，这两个CNV的神经心理学评估还没有报道。方法：本研究调查了62名缺失携带者、44名复制携带者和71名家庭内对照受试者16p11.2基因座的基因组拷贝数与认知领域评估的关系。结果：缺失和复制携带者智商降低，但我们在这些相互关联的CNV中表现出相反的认知特征。缺失携带者存在严重的语音和抑制技能障碍，超出了他们的智商水平。相比之下，在言语记忆和语音方面，数据可能表明，复制携带者的表现优于智商水平相同的家庭内对照受试者。这一发现让人想起了在自闭症谱系障碍中观察到的特殊的孤立技能以及反差的语言表现。有些领域，如视觉空间和工作记忆，除了智商下降的影响外，不受16p11.2基因座的影响。神经影像分析显示，抑制的测量与先前被认为对16p11.2 CNV敏感的神经解剖结构不同。结论：对相互CNV的同时研究表明，16p11.2基因组基因座根据基因组拷贝数调节特定的认知技能。有必要进行进一步的研究来重复这些发现，并阐明调节这些认知表现的分子机制。
BACKGROUND: Deletions and duplications of the 16p11.2 BP4-BP5 locus are prevalent copy number variations (CNVs), highly associated with autism spectrum disorder and schizophrenia. Beyond language and global cognition, neuropsychological assessments of these two CNVs have not yet been reported.METHODS: This study investigates the relationship between the number of genomic copies at the 16p11.2 locus and cognitive domains assessed in 62 deletion carriers, 44 duplication carriers, and 71 intrafamilial control subjects.RESULTS: IQ is decreased in deletion and duplication carriers, but we demonstrate contrasting cognitive profiles in these reciprocal CNVs. Deletion carriers present with severe impairments of phonology and of inhibition skills beyond what is expected for their IQ level. In contrast, for verbal memory and phonology, the data may suggest that duplication carriers outperform intrafamilial control subjects with the same IQ level. This finding is reminiscent of special isolated skills as well as contrasting language performance observed in autism spectrum disorder. Some domains, such as visuospatial and working memory, are unaffected by the 16p11.2 locus beyond the effect of decreased IQ. Neuroimaging analyses reveal that measures of inhibition covary with neuroanatomic structures previously identified as sensitive to 16p11.2 CNVs.CONCLUSIONS: The simultaneous study of reciprocal CNVs suggests that the 16p11.2 genomic locus modulates specific cognitive skills according to the number of genomic copies. Further research is warranted to replicate these findings and elucidate the molecular mechanisms modulating these cognitive performances.