Identification of KMT2D and KDM6A mutations by exome sequencing in Korean patients with Kabuki syndrome.

[kabuki syndrome]

Kabuki syndrome (KS ) (OMIM #147920 ) is a multiple congenital anomaly /mental retardation syndrome . Recently , pathogenic variants in KMT 2 D and KDM 6 A were identified as the causes of KS in 55 .8 -80 .0 % of patients . To elucidate further the molecular characteristics of Korean patients with KS , we screened a cohort of patients with clinically defined KS for mutations in KMT 2 D and KDM 6 A . Whole-exome sequencing and direct sequencing for validation were performed in 12 patients with a clinical suspicion of KS . KMT 2 D and KDM 6 A mutations were identified in 11 (91 .7 %) patients . No recurrent mutation was observed , and 10 out of the 11 mutations found were novel . KMT 2 D mutations were detected in 10 patients , including four small deletions or insertions and four nonsense and two missense mutations . One girl had a novel splice-site mutation in KDM 6 A . Each patient had a unique individual mutation . This is the first report of mutational analysis via exome sequencing in Korean patients with KS . Because the mutation -detection rate was high in this study , rigorous mutation analysis of KMT 2 D and KDM 6 A may be an important tool for the early diagnosis and genetic counseling of Korean patients with KS .