Characterization of a Novel Transcript of the EHMT1 Gene Reveals Important Diagnostic Implications for Kleefstra Syndrome
Characterization of a Novel Transcript of the EHMT1 Gene Reveals Important Diagnostic Implications for Kleefstra Syndrome
复制标题
DOI：
10.1002/humu.21523
复制
发表时间：
2011-07-01
期刊：
影响因子：
3.9
通讯作者：
Kleefstra, Tjitske
中科院分区：
文献类型：
--
作者：
Nillesen, Willy M.;Yntema, Helger G.;Kleefstra, Tjitske
Kleefstra综合征（KS）的核心表型以智力残疾、儿童张力低下和特征性面部外观为特征。这可能是由亚微观的9q34缺失或EHMT1基因功能突变的丧失引起的。值得注意的是，在3例临床怀疑为KS的患者中，分子细胞遗传学分析显示，基于NM_024757.3转录本，在EHMT1基因编码区附近存在9q34间质微缺失。由于我们在其中两名患者中发现了EHMT1单等位基因转录物，提示EHMT1单倍不足，我们假设EHMT1基因50区域中调控元件的缺失或迄今未知的编码序列可能导致与KS相容的表型。我们进一步表征了转录本NM_024757.3附近缺失的分子含量，并证实存在一个新的预测开放阅读框，包括27个编码外显子（NM_024757.4）。进一步的分析表明，所有三个缺失都包括假定的EHMT1基因的新第一外显子。随后对75名先前未检测到EHMT1畸变的个体进行的测试显示，另外一个病例的缺失仅包含该基因的这50部分。这些结果对KS的遗传筛选和研究EHMT1的功能意义具有重要意义。[j] .农业科学，2011。(C) 2011 Wiley-Liss, Inc。
The core phenotype of Kleefstra syndrome (KS) is characterized by intellectual disability, childhood hypotonia, and a characteristic facial appearance. This can be caused by either submicroscopic 9q34 deletions or loss of function mutations of the EHMT1 gene. Remarkably, in three patients with a clinical suspicion of KS, molecular cytogenetic analysis revealed an interstitial 9q34 microdeletion proximal to the coding region of the EHMT1 gene based on the NM_024757.3 transcript. Because we found a mono-allelic EHMT1 transcript suggestive for haploinsufficiency of EHMT1 in two of these patients tested, we hypothesized that a deletion of regulatory elements or so far unknown coding sequences in the 50 region of the EHMT1 gene, might result in a phenotype compatible with KS. We further characterized the molecular content of deletions proximal to the transcript NM_024757.3 and confirmed presence of a novel predicted open reading frame comprising 27 coding exons (NM_024757.4). Further analysis showed that all three deletions included the presumed novel first exon of the EHMT1 gene. Subsequent testing of 75 individuals without previously detectable EHMT1 aberrations showed one additional case with a deletion comprising only this 50 part of the gene. These results have important implications for the genetic screening of KS and for studies of the functional significance of EHMT1. Hum Mutat 32:853-859, 2011. (C) 2011 Wiley-Liss, Inc.