Inflammatory skin and bowel disease linked to ADAM17 deletion


  • D.C. Blaydon
  • P. Biancheri
  • W.L. Di
  • V. Plagnol
  • R.M. Cabral
  • M.A. Brooke
  • D.A. van Heel
  • F. Ruschendorf
  • M. Toynbee
  • A. Walne
  • E.A. O'Toole
  • J.E. Martin
  • K. Lindley
  • T. Vulliamy
  • D.J. Abrams
  • T.T. MacDonald
  • J.I. Harper
  • D.P. Kelsell


  • New England Journal of Medicine


  • N Engl J Med 365 (16): 1502-1508


  • 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.