Inflammatory skin and bowel disease linked to ADAM17 deletion.
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.).
Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Diana C
DC
Blaydon
Paolo
P
Biancheri
Wei-Li
WL
Di
Vincent
V
Plagnol
Rita M
RM
Cabral
Matthew A
MA
Brooke
David A
DA
van Heel
Franz
F
Ruschendorf
Mark
M
Toynbee
Amanda
A
Walne
Edel A
EA
O'Toole
Joanne E
JE
Martin
Keith
K
Lindley
Tom
T
Vulliamy
Dominic J
DJ
Abrams
Thomas T
TT
MacDonald
John I
JI
Harper
David P
DP
Kelsell
D051722:ADAM Proteins / Q000235:genetics*; D000072198:ADAM17 Protein; D000293:Adolescent; D002648:Child; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008297:Male; D009205:Myocarditis / Q000235:genetics / Q000821:virology; D010375:Pedigree; D017384:Sequence Deletion; D012871:Skin Diseases / Q000235:genetics*
D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human