Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
N Engl J Med. 2011 Oct 20;365(16):1502-8. doi: 10.1056/NEJMoa1100721.
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 α [TNF-α]-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-1β and interleukin-6 but impaired release of TNF-α. 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.).
我们对一对患有常染色体隐性新生儿炎症性皮肤和肠道疾病的兄妹进行了遗传和免疫组织化学研究。该女孩于 12 岁时因细小病毒 B19 相关心肌炎突然死亡；她的哥哥患有轻度心肌病。我们发现 ADAM17 中的功能丧失突变，ADAM17 编码解整合素金属蛋白酶 17（也称为肿瘤坏死因子α[TNF-α]-转化酶，或 TACE），可能是这种综合征的原因。从 17 岁的哥哥身上获得的外周血单核细胞（PBMC）显示出高水平的脂多糖诱导产生白细胞介素-1β和白细胞介素-6，但 TNF-α的释放受损。尽管反复发生皮肤感染，但这名年轻人过着相对正常的生活。（由 Barts 和伦敦慈善基金会以及欧盟第七框架计划资助）。
