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

Abstract

Kabuki syndrome (KS) (OMIM#147920) is a multiple congenital anomaly/mental

retardation syndrome. Recently, pathogenic variants in KMT2D and KDM6A 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 KMT2D and KDM6A. Whole-exome

sequencing and direct sequencing for validation were performed in 12 patients

with a clinical suspicion of KS. KMT2D and KDM6A mutations were identified in 11

(91.7%) patients. No recurrent mutation was observed, and 10 out of the 11

mutations found were novel. KMT2D 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 KDM6A. 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 KMT2D and KDM6A may be an

important tool for the early diagnosis and genetic counseling of Korean patients

with KS.