Inflammatory skin and bowel disease linked to ADAM17 deletion

Diana C. Blaydon, Paolo Biancheri, Wei Li Di, Vincent Plagnol, Rita M. Cabral, Matthew A. Brooke, David A. Van Heel, Franz Ruschendorf, Mark Toynbee, Amanda Walne, Edel A. O'Toole, Joanne E. Martin, Keith Lindley, Tom Vulliamy, Dominic J. Abrams, Thomas T. MacDonald, John I. Harper, David P. Kelsell

Research output: Contribution to journalArticlepeer-review


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.)

Original languageEnglish
Pages (from-to)1502-1508
Number of pages7
JournalNew England Journal of Medicine
Issue number16
Publication statusPublished - Oct 20 2011

ASJC Scopus subject areas

  • Medicine(all)


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