Inflammatory Skin and Bowel Disease Linked to ADAM17 Deletion
Inflammatory Skin and Bowel Disease Linked to ADAM17 Deletion
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DOI：
10.1056/nejmoa1100721
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发表时间：
2011-10-20
影响因子：
158.5
通讯作者：
Kelsell, David P.
中科院分区：
文献类型：
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作者：
Blaydon, Diana C.;Biancheri, Paolo;Kelsell, David P.
我们对一对患有常染色体隐性新生儿皮肤和肠道炎症的兄妹进行了遗传和免疫组织化学研究。该女童12岁时因细小病毒b19相关心肌炎突然死亡；她哥哥有轻微的心肌病。我们在ADAM17中发现了一个功能缺失突变，该突变编码一种崩解素和金属蛋白酶17（也称为肿瘤坏死因子α [tnf - α]转换酶，或TACE），这可能是导致该综合征的原因。从兄弟17岁时获得的外周血单个核细胞（PBMCs）显示高水平的脂多糖诱导的白细胞介素-1 β和白细胞介素-6的产生，但tnf - α的释放受损。尽管反复的皮肤感染，这个年轻人过着相对正常的生活。（由巴茨和伦敦慈善机构以及欧盟委员会第七框架计划资助。）
We performed genetic and immunohistochemical studies in a sister and brother with autosomal recessive neonatal inflammatory skin and bowel lesions. The girl died suddenly at 12 years of age from parvovirus B19-associated myocarditis; her brother had mild cardiomyopathy. We identified a loss-of-function mutation in ADAM17, which encodes a disintegrin and metalloproteinase 17 (also called tumor necrosis factor alpha [TNF-alpha]-converting enzyme, or TACE), as the probable cause of this syndrome. Peripheral-blood mononuclear cells (PBMCs) obtained from the brother at 17 years of age showed high levels of lipopolysaccharide-induced production of interleukin-1 beta and interleukin-6 but impaired release of TNF-alpha. Despite repeated skin infections, this young man has led a relatively normal life. (Funded by Barts and the London Charity and the European Commission Seventh Framework Programme.)