Abstract：
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.
摘要：
基因表达的精确调节对于正确的神经发育很重要。影响EHMT1基因的9q34.3缺失导致称为Kleefstra综合征的综合征性神经发育障碍。相比之下,包含EHMT1的9q34.3基因座的重复被认为会导致发育障碍，但是只有有限的信息可用。我们已经确定了来自10个不相关家庭的15个人，9q34.3复制大小<1.5Mb时，完全包含EHMT1。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。这些人并没有始终如一地表现出畸形特征，先天性异常,或生长异常。DNA甲基化分析显示，包含EHMT1的9q34.3重复病例的DNAm谱较弱，这可能会将大多数受影响的病例与对照分离。这项研究表明，包括EHMT1基因在内的9q34.3重复个体存在轻度非综合征性神经发育障碍，DNA甲基化变化不同于Kleefstra综合征。
