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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, C2
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
2013 Impact Factor: 2.048
 
DOIhttp://dx.doi.org/10.1002/ajmg.a.35570
 
DC FieldValue
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.eissn1552-4833
 
dc.identifier.epage2381
 
dc.identifier.hkuros201969
 
dc.identifier.issn1552-4825
2013 Impact Factor: 2.048
 
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
 
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<contributor.author>Hinek, A</contributor.author>
<contributor.author>Keating, S</contributor.author>
<contributor.author>Weksberg, R</contributor.author>
<contributor.author>Shah, V</contributor.author>
<contributor.author>Blaser, S</contributor.author>
<contributor.author>Hawkins, C</contributor.author>
<contributor.author>Chitayat, D</contributor.author>
<date.accessioned>2012-07-16T09:48:42Z</date.accessioned>
<date.available>2012-07-16T09:48:42Z</date.available>
<date.issued>2012</date.issued>
<identifier.citation>American Journal of Medical Genetics. Part A, 2012, v. 158A n. 10, p. 2373-2381</identifier.citation>
<identifier.issn>1552-4825</identifier.issn>
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<description.abstract>We 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&apos;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. &#169; 2012 Wiley Periodicals, Inc.</description.abstract>
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<rights>American Journal of Medical Genetics. Part A. Copyright &#169; John Wiley &amp; Sons, Inc.</rights>
<subject>Metalloproteinase (MMP)</subject>
<subject>Overgrowth</subject>
<subject>Tissue inhibitors of metalloproteinase (TIMP)</subject>
<subject>Chondroitin sulfate</subject>
<subject>Collagen type 1</subject>
<subject>Chondroitin sulfate</subject>
<subject>Doxycycline</subject>
<subject>Enoxaparin</subject>
<subject>Nitric oxide</subject>
<subject>Stromelysin</subject>
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Author Affiliations
  1. University of Toronto
  2. Hospital for Sick Children University of Toronto