Mutation of Membrane Type-1 Metalloproteinase, MT1-MMP, Causes the Multicentric Osteolysis and Arthritis Disease Winchester Syndrome
In: American journal of human genetics, Jg. 91 (2012), Heft 3, S. 572-576
Online
academicJournal
- print, 11 ref
Zugriff:
The vanishing bone syndromes represent a group of rare skeletal disorders characterized by osteolysis and joint destruction, which can mimic severe rheumatoid arthritis. Winchester syndrome was one of the first recognized autosomal-recessive, multicentric forms of the disorder. It was originally described nearly 50 years ago in two sisters with a severe crippling osteolysis. Using cultured fibroblasts from the proband, we have now identified homozygous mutations in membrane type-1 metalloproteinase (MT1-MMP or MMP14). We demonstrate that the resulting hydrophobic-region signal-peptide substitution (p.Thr17Arg) decreases MT1-MMP membrane localization with consequent impairment of pro-MMP2 activation, and we propose a structure-based mechanism for this effect.
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Mutation of Membrane Type-1 Metalloproteinase, MT1-MMP, Causes the Multicentric Osteolysis and Arthritis Disease Winchester Syndrome
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Autor/in / Beteiligte Person: | EVANS, Brad R ; MOSIG, Rebecca A ; LOBL, Mollie ; MARTIGNETTI, Chiara R ; CAMACHO, Catalina ; GRUM-TOKARS, Valerie ; GLUCKSMAN, Marc J ; MARTIGNETTI, John A |
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Zeitschrift: | American journal of human genetics, Jg. 91 (2012), Heft 3, S. 572-576 |
Veröffentlichung: | Cambridge, MA: Cell Press, 2012 |
Medientyp: | academicJournal |
Umfang: | print, 11 ref |
ISSN: | 0002-9297 (print) |
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