Decreased expression in nuclear factor-kB essential modulator due to a novel splice-site mutation causes X-linked ectodermal dysplasia with immune- deficiency
Decreased expression in nuclear factor-kB essential modulator due to a novel splice-site mutation causes X-linked ectodermal dysplasia with immune- deficiency
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由于新的剪接位点突变导致核因子-kB 必需调节剂表达减少，导致 X 连锁外胚层发育不良并伴有免疫缺陷
DOI：
10.1007/s10875-011-9560-4
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
M.
中科院分区：
文献类型：
--
作者：
Karakawa;S.;Okada;S.;Tsumura;M.;Mizoguchi;Y.;Hara;K.;Ohno;N.;Yasunaga;S.;Ohtsubo M.;Kawai;T.;Nishikimori;R.;Sakaguchi;T.;Hata;I.;Sakura;N.;Takihara;Y. & Kobayashi;M.
X-linked ectodermal dysplasia with immunodeficiency (XL-ED-ID) is caused by hypomorphic mutations inNEMO, 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 inNEMOin 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.
