KDM6A Point Mutations Cause Kabuki Syndrome

Abstract

Kabuki syndrome (KS) is a rare congenital anomaly syndrome characterized by a unique facial appearance, growth retardation, skeletal abnormalities, and intellectual disability. In 2010, MLL2 was identified as a causative gene. On the basis of published reports, 55-80% of KS cases can be explained by MLL2 abnormalities. Recently, de novo deletion of KDM6A has been reported in three KS patients, but point mutations of KDM6A have never been found. In this study, we investigated KDM6A in 32 KS patients without an MLL2 mutation. We identified two nonsense mutations and one 3-bp deletion of KDM6A in three KS cases. This is the first report of KDM6A point mutations associated with KS.

A novel de novo mutation involving the MLL2 gene in a Kabuki syndrome patient presenting with seizures

“…Since then there have been several reports of patient series describing MLL2 mutations in 52-76% of the cases [9][10][11][22][23][24] . MLL2 is a 36.3 kb gene located on chromosome 12q13.12 21 , and encodes a protein of 5537 amino acids which is located in a multiprotein complex.…”

“…Although it has been first described in the Japanese population, there have been numerous reports from other ethnic groups 4 , including patients of Turkish descent [5][6][7][8] . It generally occurs because of a "de novo" mutation, involving either the myeloid/ lymphoid or mixed-lineage leukemia 2 (MLL2) gene 9 or less frequently the lysine (K)-specific demethylase 6A (KDM6A) gene 10,11 . Here we report on a Turkish KS patient with epilepsy carrying a novel heterozygous mutation in the MLL2 gene.…”

Diagnóstico clínico en el síndrome de Kabuki: fenotipo y anomalías asociadas en dos casos nuevos

“…• Lenguaje: el retraso en la adquisición del len- Schrander-Stumpel et al 8 Sanlaville et al 9 Micale et al guaje se observa en casi todos los pacientes con SK. En el caso de fisura y/o incompetencia velopalatina, deben ser remitidos a cirugía maxilofacial y rehabilitación fonoaudiológica.…”

“…5,6 Existe una variante denominada Kabuki tipo II, con mutaciones descriptas en el gen KDM6A (Xp11.3), con un fenotipo similar, pero con un patrón de herencia dominante ligado al cromosoma X. 7,8 El objetivo de este trabajo es describir dos pacientes con diagnóstico clínico de síndrome de Kabuki, que consultaron por discapacidad intelectual, destacando los hallazgos fenotípicos y malformaciones asociadas.…”

Desvio de inativação do cromossomo X em mulheres brasileiras sem histórico familiar para deficiência intelectual ligada ao X

“…As mutações constitucionais do gene KDM6A também são apontadas como causais da Síndrome de Kabuki, a qual se caracteriza por anormalidades esqueléticas, baixa estatura e deficiência intelectual moderada a profunda (Miyake, 2012;Lederer, 2012).…”