title: Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome.
abstract: 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.
authors.affiliation: Centre de Génétique Humaine, Institut de Pathologie et Génétique, Charleroi, Belgium. damien.lederer@ipg.be
authors.forename: Damien
authors.initials: D
authors.lastname: Lederer
authors.forename: Bernard
authors.initials: B
authors.lastname: Grisart
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Digilio
authors.forename: Valérie
authors.initials: V
authors.lastname: Benoit
authors.forename: Marianne
authors.initials: M
authors.lastname: Crespin
authors.forename: Sophie Claire
authors.initials: SC
authors.lastname: Ghariani
authors.forename: Isabelle
authors.initials: I
authors.lastname: Maystadt
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Christine
authors.initials: C
authors.lastname: Verellen-Dumoulin
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D001483:Base Sequence; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D002658:Developmental Disabilities / Q000235:genetics; D005145:Face / Q000002:abnormalities; D005260:Female; D017353:Gene Deletion; D006402:Hematologic Diseases / Q000235:genetics* / Q000378:metabolism; D056466:Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015837:Vestibular Diseases / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C120898:KMT2D protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D056466:Histone Demethylases; C523998:KDM6A protein, human