Immunologic Assessment and KMT2D mutation detection in Kabuki Syndrome.

TitleImmunologic Assessment and KMT2D mutation detection in Kabuki Syndrome.
Publication TypeJournal Article
Year of Publication2014
AuthorsLin J-L, Lee W-I, Huang J-L, Chen PK-T, Chan K-C, Lo L-J, You Y-J, Shih Y-F, Tseng T-Y, Wu M-C
JournalClin Genet
Date Published2014 Aug 21

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 nine-year study period (2005-2013). All had Kabuki faces, cleft palate, developmental delays, mental retardation, and 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 of the patients had KMT2D mutations and ten novel mutations of R1252X, R1757X, Q4013X, G5379X, R5432X, Y1998C, E5425K, R5432W, R5500W, and P2550R fs2604X. 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.

Alternate JournalClin. Genet.
Citation Key1508
PubMed ID25142838