Deletions and duplications of the distal region of the long arm of chromosome 1 are associated with brain abnormalities and developmental delay. Because duplications are less frequent than deletions, no detailed account of the cognitive profile of the affected people is available, particularly, regarding their language (dis)abilities. In this paper we report on the cognitive and language features of a girl with one of the smallest interstitial duplications ever described in this region, affecting to 1q42.3q43 (arr[hg19] 1q42.3q43(235,963,632-236,972,276)x3). Standardized tests as well as the analysis of her language use in natural settings suggest that the proband's speech is severely impaired, exhibiting dysarthric-like features, with speech problems also resulting from a phonological deficit boiling down to a verbal auditory memory deficit. Lexical and grammatical knowledge are also impaired, impacting negatively on both expressive and receptive abilities, seemingly as a consequence of the phonological deficit. Still, her pragmatic abilities seem to be significantly spared, granting her a good command on the principles governing conversational exchanges. In silico analyses (literature mining, network analysis) and in vitro analyses (microarray) point to several genes as potential candidates for the observed deficits in the language domain. These include one gene within the duplicated region (LYST), one predicted functional partner (CMIP), and three genes outside the 1q42.3q43 region, which are all highly expressed in the cerebellum: DDIT4 and SLC29A1, found strongly downregulated in the proband compared to their healthy parents, and CNTNAP3, found strongly upregulated.

中文翻译：

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1q42.3q43中有微复制的语言障碍

1号染色体长臂远端区域的缺失和重复与大脑异常和发育延迟有关。由于重复的频率比删除的频率低，因此无法获得受影响人群的认知特征的详细说明，尤其是关于他们的语言（残疾）能力的信息。在本文中，我们报告了一个女孩的认知和语言特征，该女孩是该地区有史以来最小的间质重复之一，影响到1q42.3q43（arr [hg19] 1q42.3q43（235,963,632-236,972,276）x3）。标准化的测试以及对她在自然环境中使用语言的分析表明，先证者的言语受到严重损害，表现出构音障碍样的特征，语音问题也源于语音缺陷逐渐演变为口头听觉记忆缺陷。词汇和语法知识也受到损害，这似乎是由于语音缺陷导致的对表达和接受能力的负面影响。尽管如此，她的务实能力似乎仍然得到了极大的节省，这使她对管理对话交流的原则有了很好的指挥。计算机分析（文献挖掘，网络分析）和体外分析（微阵列）指出，几种基因可能是语言域中观察到的缺陷的潜在候选者。这些基因包括一个在重复区域（LYST）内的基因，一个预测的功能伙伴（CMIP）和在1q42.3q43区域外的三个基因，它们在小脑中都高度表达：DDIT4和SLC29A1，在先证者中被强烈下调他们的健康父母和CNTNAP3被强烈上调。