title: Immunologic assessment and KMT2D mutation detection in Kabuki syndrome.
abstract: 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.
authors.affiliation: Division of Genetics and Endocrinology.
authors.forename: J-L
authors.initials: JL
authors.lastname: Lin
authors.affiliation: Primary Immunodeficiency Care and Research (PICAR) Institute.|Division of Allergy, Asthma and Rheumatology, Department of Pediatrics.
authors.forename: W-I
authors.initials: WI
authors.lastname: Lee
authors.affiliation: Primary Immunodeficiency Care and Research (PICAR) Institute.|Division of Allergy, Asthma and Rheumatology, Department of Pediatrics.
authors.forename: J-L
authors.initials: JL
authors.lastname: Huang
authors.affiliation: Division of Plasty, Department of Surgery.
authors.forename: P K-T
authors.initials: PK
authors.lastname: Chen
authors.affiliation: Division of Ear, Nose and Throat, Department of Surgery, Chang Gung University College of Medicine and Chang Gung Children's and Memorial Hospital, Taoyuan, Taiwan.
authors.forename: K-C
authors.initials: KC
authors.lastname: Chan
authors.affiliation: Division of Plasty, Department of Surgery.
authors.forename: L-J
authors.initials: LJ
authors.lastname: Lo
authors.affiliation: Division of Genetics and Endocrinology.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: You
authors.affiliation: Primary Immunodeficiency Care and Research (PICAR) Institute.
authors.forename: Y-F
authors.initials: YF
authors.lastname: Shih
authors.affiliation: Primary Immunodeficiency Care and Research (PICAR) Institute.
authors.forename: T-Y
authors.initials: TY
authors.lastname: Tseng
authors.affiliation: Division of Genetics and Endocrinology.
authors.forename: M-C
authors.initials: MC
authors.lastname: Wu
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D004406:Dysgammaglobulinemia / Q000235:genetics / Q000276:immunology; D005145:Face / Q000002:abnormalities*; D005260:Female; D006402:Hematologic Diseases / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010641:Phenotype; D015837:Vestibular Diseases / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; C120898:KMT2D protein, human; D009363:Neoplasm Proteins
keywords: KMT2D; Kabuki or Niikawa-Kuroki syndrome; MLL2; common variable immunodeficiency disease; emigrant naïve T and B cells; memory B-cell; memory T-cell; recurrent otitis media