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

J Hum Genet. 2014 Jun;59(6):321-5. doi: 10.1038/jhg.2014.25. Epub 2014 Apr 17.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Exome*
  • Face / abnormalities*
  • Female
  • Hematologic Diseases / genetics*
  • Histone Demethylases / genetics*
  • Humans
  • Infant
  • Male
  • Mutation
  • Neoplasm Proteins / genetics*
  • Nuclear Proteins / genetics*
  • Republic of Korea
  • Vestibular Diseases / genetics*

Substances

  • DNA-Binding Proteins
  • KMT2D protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Histone Demethylases
  • KDM6A protein, human

Supplementary concepts

  • Kabuki syndrome