Deletion of KDM6A, a Histone Demethylase Interacting with MLL2, in Three Patients with Kabuki Syndrome
Deletion of KDM6A, a Histone Demethylase Interacting with MLL2, in Three Patients with Kabuki Syndrome
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DOI：
10.1016/j.ajhg.2011.11.021
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发表时间：
2012-01-13
影响因子：
9.8
通讯作者：
Verellen-Dumoulin, Christine
中科院分区：
文献类型：
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作者：
Lederer, Damien;Grisart, Bernard;Verellen-Dumoulin, Christine
歌舞伎综合征(KS)是一种罕见的遗传性疾病，会导致发育迟缓和先天性畸形。自从MLL2突变被确定为KS的主要原因以来，已在56%-76%的受影响个体中发现了此类突变，这表明可能存在与KS相关的其他基因。在这里，我们描述了三个KS患者，X染色体基因KDM6A部分或完全缺失，KDM6A编码与MLL2相互作用的组蛋白去甲基酶。虽然KDM6A逃脱了X失活，但我们发现了一种扭曲的X失活模式，在大多数细胞中，缺失的X染色体被失活。这项研究发现KDM6A突变是KS的另一个原因，并强调了组蛋白甲基酶和组蛋白去甲基酶在多发性先天性异常和智力残疾综合征中日益增长的作用。
Kabuki syndrome (KS) is a rare genetic disease that causes developmental delay and congenital anomalies. Since the identification of MLL2 mutations as the primaly cause of KS, such mutations have been identified in 56%-76% of affected individuals, suggesting that there may be additional genes associated with KS. Here, we describe three KS individuals with de novo partial or complete deletions of an X chromosome gene, KDM6A, that encodes a histone demethylase that interacts with MLL2. Although KDM6A escapes X inactivation, we found a skewed X inactivation pattern, in which the deleted X chromosome was inactivated in the majority of the cells. This study identifies KDM6A mutations as another cause of KS and highlights the growing role of histone methylases and histone demethylases in multiple-congenital-anomaly and intellectual-disability syndromes.