Immunologic assessment and KMT2D mutation detection in Kabuki syndrome

J. L. Lin, Wen I. Lee*, J. L. Huang, P. K.T. Chen, K. C. Chan, L. J. Lo, Y. J. You, Y. F. Shih, T. Y. Tseng, M. C. Wu

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

42 Scopus citations


Kabuki or Niikawa-Kuroki syndrome (KS) is a rare disorder with multiple malformations and recurrent infections, especially otitis media. This study aimed to investigate the genetic defects in Kabuki syndrome and determine if immune status is related to recurrent otitis media. Fourteen patients from 12 unrelated families were enrolled in the 9-year study period (2005-2013). All had Kabuki faces, cleft palate, developmental delay, mental retardation, and the short fifth finger. Recurrent otitis media (12/14) and hearing impairment (8/14) were also more common features. Immunologic analysis revealed lower memory CD19+ cells (11/13), lower memory CD4+ cells (8/13), undetectable anti-HBs antibodies (7/13), and antibody deficiency (7/13), including lower IgA (4), IgG (2), and IgG2 (1). Naïve emigrant lymphocytes, lymphocyte proliferation function, complement activity, and superoxide production in polymorphonuclear cells were all normal. All the patients had KMT2D mutations and 10 novel mutations of R1252X, R1757X,Y1998C, P2550R fs2604X, Q4013X, G5379X, E5425K, R5432X, R5432W, and R5500W. Resembling the phenotype of common variable immunodeficiency, KS patients with antibody deficiency, decreased memory cells, and poor vaccine response increased susceptibility to recurrent otitis media. Large-scale prospective studies are warranted to determine if regular immunoglobulin supplementation decreases the frequency of otitis media and severity of hearing impairment.

Original languageEnglish
Pages (from-to)255-260
Number of pages6
JournalClinical Genetics
Issue number3
StatePublished - 01 09 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


  • Common variable immunodeficiency disease
  • Emigrant naïve T and B cells
  • KMT2D
  • Kabuki or Niikawa-Kuroki syndrome
  • MLL2
  • Memory B-cell
  • Memory T-cell
  • Recurrent otitis media


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