Inflammatory skin and bowel disease linked to ADAM17 deletion.
Blaydon DC., Biancheri P., Di WL., Plagnol V., Cabral RM., Brooke MA., van Heel DA., Ruschendorf F., Toynbee M., Walne A., O'Toole EA., Martin JE., Lindley K., Vulliamy T., Abrams DJ., MacDonald TT., Harper JI., Kelsell DP.
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.).