title: X-linked ectodermal dysplasia and immunodeficiency caused by reversion mosaicism of NEMO reveals a critical role for NEMO in human T-cell development and/or survival.
abstract: X-linked ectodermal dysplasia and immunodeficiency (XL-EDA-ID) is an X-linked recessive disease caused by a mutation in the nuclear factor-kappaB (NF-kappaB) essential modulator (NEMO). Here we report an XL-EDA-ID patient with atypical features of very few naive-phenotype T cells and defective mitogen-induced proliferation of peripheral blood mononuclear cells (PBMCs). The patient's NEMO defect was diagnosed by flow cytometric analysis of intracellular NEMO staining. Specific cell lineages (monocytes and neutrophils) expressed reduced levels of NEMO, but 2 populations of T, B, and NK cells were detected with normal and reduced expression of NEMO. Genomic analysis revealed that duplication of a 4.4-kb sequence ranging from intron 3 to exon 6 caused the reduced expression of NEMO. Polymorphism analysis showed that the patient's B- and T-cell lines with reduced and normal expression of NEMO had the same X chromosome, indicating that the somatic mosaicism was not due to fetomaternal transfusion but was most likely due to postzygotic reversion. This XLEDA-ID case adds to our understanding of NEMO biology, indicating that NEMO is critical for T-cell development and/or survival in humans as well as in mice.
authors.affiliation: Department of Pediatrics and Laboratory Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo, Kyoto 606-8507, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Nishikomori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akutagawa
authors.forename: Kyoko
authors.initials: K
authors.lastname: Maruyama
authors.forename: Mami
authors.initials: M
authors.lastname: Nakata-Hizume
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Ohmori
authors.forename: Kazunori
authors.initials: K
authors.lastname: Mizuno
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yachie
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yasumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kusunoki
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000097:blood; D001483:Base Sequence; D015415:Biomarkers; D002470:Cell Survival; D002648:Child; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D051550:I-kappa B Kinase; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology*; D008297:Male; D051379:Mice; D009030:Mosaicism; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000097:blood; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology*; D014960:X Chromosome / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D016207:Cytokines; D017931:DNA Primers; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse