title: Decreased expression in nuclear factor-κB essential modulator due to a novel splice-site mutation causes X-linked ectodermal dysplasia with immunodeficiency.
abstract: X-linked ectodermal dysplasia with immunodeficiency (XL-ED-ID) is caused by hypomorphic mutations in NEMO, which encodes nuclear factor-kappaB (NF-κB) essential modulator. We identified a novel mutation, 769-1 G>C, at the splicing acceptor site of exon 7 in NEMO in a Japanese patient with XL-ED-ID. Although various abnormally spliced NEMO messenger RNAs (mRNAs) were observed, a small amount of wild-type (WT) mRNA was also identified. Decreased NEMO protein expression was detected in various lineages of leukocytes. Although one abnormally spliced NEMO protein showed residual NF-κB transcription activity, it did not seem to exert a dominant-negative effect against WT-NEMO activity. CD4(+) T cell proliferation was impaired in response to measles and mumps, but not rubella. These results were consistent with the clinical and laboratory findings of the patient, suggesting the functional importance of NEMO against specific viral infections. The 769-1 G>C mutation is responsible for decreased WT-NEMO protein expression, resulting in the development of XL-ED-ID.
authors: Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors: Shuhei
authors: S
authors: Karakawa
authors: Satoshi
authors: S
authors: Okada
authors: Miyuki
authors: M
authors: Tsumura
authors: Yoko
authors: Y
authors: Mizoguchi
authors: Norioki
authors: N
authors: Ohno
authors: Shin'ichiro
authors: S
authors: Yasunaga
authors: Motoaki
authors: M
authors: Ohtsubo
authors: Tomoki
authors: T
authors: Kawai
authors: Ryuta
authors: R
authors: Nishikomori
authors: Takemasa
authors: T
authors: Sakaguchi
authors: Yoshihiro
authors: Y
authors: Takihara
authors: Masao
authors: M
authors: Kobayashi
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D001424:Bacterial Infections / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D048708:Cell Growth Processes / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D015536:Down-Regulation / Q000235:genetics; D004476:Ectodermal Dysplasia / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D016130:Immunophenotyping; D007564:Japan; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D000081207:Primary Immunodeficiency Diseases; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012008:Recurrence; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014777:Virus Diseases / Q000235:genetics* / Q000276:immunology
chemical_list: C491731:IKBKG protein, human; D020033:Protein Isoforms; D051550:I-kappa B Kinase