Precise regulation of gene expression is important for correct neurodevelopment. 9q34.3 deletions affecting the EHMT1 gene result in a syndromic neurodevelopmental disorder named Kleefstra syndrome. In contrast, duplications of the 9q34.3 locus encompassing EHMT1 have been suggested to cause developmental disorders, but only limited information has been available. We have identified 15 individuals from 10 unrelated families, with 9q34.3 duplications <1.5 Mb in size, encompassing EHMT1 entirely. Clinical features included mild developmental delay, mild intellectual disability or learning problems, autism spectrum disorder, and behavior problems. The individuals did not consistently display dysmorphic features, congenital anomalies, or growth abnormalities. DNA methylation analysis revealed a weak DNAm profile for the cases with 9q34.3 duplication encompassing EHMT1, which could segregate the majority of the affected cases from controls. This study shows that individuals with 9q34.3 duplications including EHMT1 gene present with mild non‐syndromic neurodevelopmental disorders and DNA methylation changes different from Kleefstra syndrome.

中文翻译：

---

改进 9q34.3 微重复综合征揭示了与独特的整体 DNA 甲基化谱相关的轻度神经发育特征

基因表达的精确调控对于正确的神经发育非常重要。9q34.3 缺失影响EHMT1基因导致一种称为克利夫斯特拉综合征的综合征性神经发育障碍。相反，9q34.3 基因座的重复包含EHMT1已被认为会导致发育障碍，但可获得的信息有限。我们已经识别出来自 10 个无关家族的 15 个人，其 9q34.3 重复大小 <1.5 Mb，包括EHMT1完全。临床特征包括轻度发育迟缓、轻度智力障碍或学习问题、自闭症谱系障碍和行为问题。这些个体并没有始终表现出畸形特征、先天异常或生长异常。DNA 甲基化分析显示，9q34.3 重复病例的 DNAm 谱较弱，包括EHMT1，这可以将大多数受影响的病例与控制区分开。这项研究表明，具有 9q34.3 重复的个体包括EHMT1基因存在轻度非综合征性神经发育障碍和与 Kleefstra 综合征不同的 DNA 甲基化变化。