MLL2 and KDM6A mutations in patients with Kabuki syndrome.

[kabuki syndrome]

Kabuki syndrome is a congenital anomaly syndrome characterized by developmental delay , intellectual disability , specific facial features including long palpebral fissures and ectropion of the lateral third of the lower eyelids , prominent digit pads , and skeletal and visceral abnormalities . Mutations in MLL 2 and KDM 6 A cause Kabuki syndrome . We screened 81 individuals with Kabuki syndrome for mutations in these genes by conventional methods (n = 58 ) and /or targeted resequencing (n = 45 ) or whole exome sequencing (n = 5 ). We identified a mutation in MLL 2 or KDM 6 A in 50 (61 .7 %) and 5 (6 .2 %) cases , respectively . Thirty -five MLL 2 mutations and two KDM 6 A mutations were novel . Non-protein truncating-type MLL 2 mutations were mainly located around functional domains , while truncating-type mutations were scattered through the entire coding region . The facial features of patients in the MLL 2 truncating-type mutation group were typical based on those of the 10 originally reported patients with Kabuki syndrome ; those of the other groups were less typical . High arched eyebrows , short fifth finger , and hypotonia in infancy were more frequent in the MLL 2 mutation group than in the KDM 6 A mutation group . Short stature and postnatal growth retardation were observed in all individuals with KDM 6 A mutations , but in only half of the group with MLL 2 mutations .