TY - JOUR
T1 - Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with kabuki syndrome
AU - Lederer, Damien
AU - Grisart, Bernard
AU - Digilio, Maria Cristina
AU - Benoit, Valérie
AU - Crespin, Marianne
AU - Ghariani, Sophie Claire
AU - Maystadt, Isabelle
AU - Dallapiccola, Bruno
AU - Verellen-Dumoulin, Christine
PY - 2012/1/13
Y1 - 2012/1/13
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajhg.2011.11.021
DO - 10.1016/j.ajhg.2011.11.021
M3 - Article
C2 - 22197486
AN - SCOPUS:84855833698
VL - 90
SP - 119
EP - 124
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 1
ER -