Article: Overgrowth with increased proliferation of fibroblast and matrix metalloproteinase activity related to reduced TIMP1: a newly recognized syndrome?

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TitleOvergrowth with increased proliferation of fibroblast and matrix metalloproteinase activity related to reduced TIMP1: a newly recognized syndrome?
AuthorsChung, BHY1 2
Hinek, A2
Keating, S1
Weksberg, R2
Shah, V1
Blaser, S2
Hawkins, C
Chitayat, D1 2
KeywordsMetalloproteinase (MMP)
Overgrowth
Tissue inhibitors of metalloproteinase (TIMP)
Chondroitin sulfate
Collagen type 1
Chondroitin sulfate
Doxycycline
Enoxaparin
Nitric oxide
Stromelysin
Tissue inhibitor of metalloproteinase 1
Issue Date2012
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/journal/117928899/grouphome/home.html
CitationAmerican Journal of Medical Genetics. Part A, 2012, v. 158A n. 10, p. 2373-2381 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ajmg.a.35570
AbstractWe report on a child with prenatal onset of overgrowth associated with thick, excessive wrinkled skin and other abnormalities including cleft palate, Chiari malformation and polymicrogyria. His clinical features do not resemble any of the known reported overgrowth syndromes. Genetic evaluations, including karyotype, oligoarray, methylation-sensitive multiplex ligation-dependent probe amplification (MLPA) for 11p11.2 region, CDKN1C sequencing, GPC3 sequencing and dosage analysis, and HRAS sequencing, have been un-revealing. Immunohistochemistry done on the patient's cultured skin fibroblasts showed normally assembled elastic fibers and normal pattern of chondroitin sulfate deposition with defective deposition of Collagen I fibers. In addition, there were high levels of immuno-detectable metalloproteinase 3 (MMP3) and undetectable tissue inhibitor of metalloproteinase 1 (TIMP1). The defective collagen deposition in the fibroblast culture could be reversed by the broad spectrum MMP inhibitor, doxycycline. We also present evidence that the fibroblasts of this patient have an increased rate of cellular proliferation. We propose that this is a previously unrecognized overgrowth syndrome associated with increased cellular proliferation and defective collagen I deposition due to an imbalance between MMP and TIMP in fibroblasts. © 2012 Wiley Periodicals, Inc.
DescriptionNew Syndrome
ISSN1552-4825
2011 Impact Factor: 2.391
2011 SCImago Journal Rankings: 0.261
DOIhttp://dx.doi.org/10.1002/ajmg.a.35570
DC Field
Value
dc.contributor.authorChung, BHY
dc.contributor.authorHinek, A
dc.contributor.authorKeating, S
dc.contributor.authorWeksberg, R
dc.contributor.authorShah, V
dc.contributor.authorBlaser, S
dc.contributor.authorHawkins, C
dc.contributor.authorChitayat, D
dc.date.accessioned2012-07-16T09:48:42Z
dc.date.available2012-07-16T09:48:42Z
dc.date.issued2012
dc.description.abstractWe report on a child with prenatal onset of overgrowth associated with thick, excessive wrinkled skin and other abnormalities including cleft palate, Chiari malformation and polymicrogyria. His clinical features do not resemble any of the known reported overgrowth syndromes. Genetic evaluations, including karyotype, oligoarray, methylation-sensitive multiplex ligation-dependent probe amplification (MLPA) for 11p11.2 region, CDKN1C sequencing, GPC3 sequencing and dosage analysis, and HRAS sequencing, have been un-revealing. Immunohistochemistry done on the patient's cultured skin fibroblasts showed normally assembled elastic fibers and normal pattern of chondroitin sulfate deposition with defective deposition of Collagen I fibers. In addition, there were high levels of immuno-detectable metalloproteinase 3 (MMP3) and undetectable tissue inhibitor of metalloproteinase 1 (TIMP1). The defective collagen deposition in the fibroblast culture could be reversed by the broad spectrum MMP inhibitor, doxycycline. We also present evidence that the fibroblasts of this patient have an increased rate of cellular proliferation. We propose that this is a previously unrecognized overgrowth syndrome associated with increased cellular proliferation and defective collagen I deposition due to an imbalance between MMP and TIMP in fibroblasts. © 2012 Wiley Periodicals, Inc.
dc.description.natureLink_to_subscribed_fulltext
dc.descriptionNew Syndrome
dc.identifier.citationAmerican Journal of Medical Genetics. Part A, 2012, v. 158A n. 10, p. 2373-2381 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ajmg.a.35570
dc.identifier.doihttp://dx.doi.org/10.1002/ajmg.a.35570
dc.identifier.epage2381
dc.identifier.hkuros201969
dc.identifier.issn1552-4825
2011 Impact Factor: 2.391
2011 SCImago Journal Rankings: 0.261
dc.identifier.issue10
dc.identifier.pmid22965799
dc.identifier.scopuseid_2-s2.0-84866505194
dc.identifier.spage2373
dc.identifier.urihttp://hdl.handle.net/10722/152804
dc.identifier.volume158A
dc.languageeng
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/journal/117928899/grouphome/home.html
dc.publisher.placeUnited States
dc.relation.ispartofAmerican Journal of Medical Genetics. Part A
dc.rightsAmerican Journal of Medical Genetics. Part A. Copyright © John Wiley & Sons, Inc.
dc.subjectMetalloproteinase (MMP)
dc.subjectOvergrowth
dc.subjectTissue inhibitors of metalloproteinase (TIMP)
dc.subjectChondroitin sulfate
dc.subjectCollagen type 1
dc.subjectChondroitin sulfate
dc.subjectDoxycycline
dc.subjectEnoxaparin
dc.subjectNitric oxide
dc.subjectStromelysin
dc.subjectTissue inhibitor of metalloproteinase 1
dc.titleOvergrowth with increased proliferation of fibroblast and matrix metalloproteinase activity related to reduced TIMP1: a newly recognized syndrome?
dc.typeArticle
Author Affiliations
  1. University of Toronto
  2. Hospital for Sick Children, Toronto