Both copy number losses and gains occur within subtelomeric 9q34 region without common breakpoints. The microdeletions cause Kleefstra syndrome (KS), whose responsible gene is EHMT1. A 9q34 duplication syndrome (9q34 DS) had been reported in literature, but it has never been characterized by a detailed molecular analysis of the gene content and endpoints. To the best of our knowledge, we report on the first patient carrying the smallest 9q34.3 duplication containing EHMT1 as the only relevant gene. We compared him with 21 reported patients described here as carrying 9q34.3 duplications encompassing the entire gene and extending within ~ 3 Mb. By surveying the available clinical and molecular cytogenetic data, we were able to discover that similar neurodevelopmental disorders (NDDs) were shared by patient carriers of even very differently sized duplications. Moreover, some facial features of the 9q34 DS were more represented than those of KS. However, an accurate in silico analysis of the genes mapped in all the duplications allowed us to support EHMT1 as being sufficient to cause a NDD phenotype. Wider patient cohorts are needed to ascertain whether the rearrangements have full causative role or simply confer the susceptibility to NDDs and possibly to identify the cognitive and behavioral profile associated with the increased dosage of EHMT1.

中文翻译：

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9q34.3微复制通过EHMT1过表达导致神经发育障碍。

拷贝数的损失和增加都发生在亚端粒9q34区域内，没有共同的断点。微缺失会导致Kleefstra综合征（KS），其负责的基因是EHMT1。文献中已经报道了9q34复制综合征（9q34 DS），但从未对基因含量和终点进行详细的分子分析来表征。据我们所知，我们的第一个病人携带含有最小9q34.3重复报告EHMT1作为唯一的相关基因。我们将他与这里描述的21名患者进行了比较，这些患者携带9q34.3重复序列，这些重复序列涵盖了整个基因并在〜3 Mb范围内延伸。通过调查可用的临床和分子细胞遗传学数据，我们能够发现相似大小的重复个体差异很大的患者携带者共享了相似的神经发育障碍（NDD）。此外，9q34 DS的某些面部特征比KS更具代表性。但是，对所有重复中定位的基因进行的精确计算机分析，使我们能够支持EHMT1足以引起NDD表型。需要更广泛的患者队列来确定重排是否具有完全的致病作用，或者仅仅是赋予NDD易感性，并可能确定与EHMT1剂量增加有关的认知和行为特征。