Deletion of KDM6A, a Histone Demethylase Interacting with MLL2, in Three Patients with Kabuki Syndrome

• Published in: American journal of human genetics Vol. 90; no. 1; pp. 119 - 124
• Main Authors: Lederer, Damien, Grisart, Bernard, Digilio, Maria Cristina, Benoit, Valérie, Crespin, Marianne, Ghariani, Sophie Claire, Maystadt, Isabelle, Dallapiccola, Bruno, Verellen-Dumoulin, Christine
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 13.01.2012; Cell Press; Elsevier
• Subjects: Abnormalities, Multiple - genetics; Abnormalities, Multiple - metabolism; Adolescent; Base Sequence; Biological and medical sciences; Child, Preschool; Chromosomes; Chromosomes, Human, X - genetics; Developmental Disabilities - genetics; DNA-Binding Proteins - metabolism; Face - abnormalities; Female; Fundamental and applied biological sciences. Psychology; Gene Deletion; Gene expression; General aspects. Genetic counseling; Genetic disorders; Genetic research; Genetics of eukaryotes. Biological and molecular evolution; Hematologic Diseases - genetics; Hematologic Diseases - metabolism; Histone Demethylases - genetics; Histone Demethylases - metabolism; Humans; Infant; Intellectual Disability - genetics; Male; Medical genetics; Medical sciences; Molecular and cellular biology; Molecular Sequence Data; Mutation; Neoplasm Proteins - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Proteins; Vestibular Diseases - genetics; Vestibular Diseases - metabolism; Chromosomal aberration; Human; Malformation; Deletion; Kabuki make-up syndrome; Genetics; Patient; Complex syndrome; Histone
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1016/j.ajhg.2011.11.021

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.