Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome.

TitleDeletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome.
Publication TypeJournal Article
Year of Publication2012
AuthorsLederer D, Grisart B, Digilio MC, Benoit V, Crespin M, Ghariani SC, Maystadt I, Dallapiccola B, Verellen-Dumoulin C
JournalAm J Hum Genet
Volume90
Issue1
Pagination119-24
Date Published2012 Jan 13
ISSN1537-6605
KeywordsAbnormalities, Multiple, Adolescent, Base Sequence, Child, Preschool, Chromosomes, Human, X, Developmental Disabilities, DNA-Binding Proteins, Face, Female, Gene Deletion, Hematologic Diseases, Histone Demethylases, Humans, Infant, Intellectual Disability, Male, Molecular Sequence Data, Neoplasm Proteins, Nuclear Proteins, Vestibular Diseases
AbstractKabuki 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.
DOI10.1016/j.ajhg.2011.11.021
Alternate JournalAm. J. Hum. Genet.
Citation Key1104
PubMed ID22197486