Centre de Génétique Humaine, Institut de Pathologie et Génétique, Charleroi, Belgium.
Am J Hum Genet. 2012 Jan 13;90(1):119-24. doi: 10.1016/j.ajhg.2011.11.021. Epub 2011 Dec 22.
Kabuki syndrome (KS) is a rare genetic disease that causes developmental delay and congenital anomalies. Since the identification of MLL2 mutations as the primary 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.
歌舞伎综合征（KS）是一种罕见的遗传疾病，可导致发育迟缓及先天异常。自 MLL2 突变被确定为 KS 的主要病因以来，约有 56%-76%的患者存在此类突变，这表明可能还有其他与 KS 相关的基因。在这里，我们描述了 3 名 KS 个体存在 X 染色体基因 KDM6A 的从头部分或完全缺失，该基因编码与 MLL2 相互作用的组蛋白去甲基酶。尽管 KDM6A 逃避 X 染色体失活，但我们发现了一种偏倚的 X 染色体失活模式，其中大多数细胞中的缺失 X 染色体失活。本研究确定 KDM6A 突变是 KS 的另一个病因，并强调了组蛋白甲基转移酶和组蛋白去甲基酶在多种先天异常和智力障碍综合征中的作用不断增加。
