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Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity

Olivier Vanakker UGent, Ludovic Martin, Dealba Gheduzzi, Bart Leroy UGent, Bart Loeys UGent, Veronica I Guerci, Dirk Matthys UGent, Sharon F Terry, Paul Coucke UGent and Ivonne Pasquali-Ronchetti, et al. (2007) JOURNAL OF INVESTIGATIVE DERMATOLOGY. 127(3). p.581-587
abstract
Data on six patients with a Pseudoxanthoma Elasticum (PXE)-like phenotype, characterized by excessive skin folding (resembling cutis laxa) and a deficiency of the vitamin K-dependent clotting factors (II, VII, IX, and X) are presented. A comparison is made between the clinical, ultrastructural, and molecular findings in these patients and those seen in classic PXE and cutis laxa, respectively. Clinical overlap with PXE is obvious from the skin manifestations of yellowish papules or leathery plaques with dot-like depressions at presentation, angioid streaks and/or ocular peau d'orange, and fragmentation and calcification of elastic fibers in the dermis. Important phenotypic differences with PXE include much more severe skin laxity with spreading toward the trunk and limbs with thick, leathery skin folds rather than confinement to flexural areas, and no decrease in visual acuity. Moreover, detailed electron microscopic analyses revealed that alterations of elastic fibers as well as their mineralization were slightly different from those in classic PXE. Molecular analysis revealed neither causal mutations in the ABCC6 gene (ATP-binding cassette subfamily C member 6), which is responsible for PXE, nor in VKORC1 (vitamin K 2,3 epoxide reductase), known to be involved in vitamin K-dependent factor deficiency. However, the GGCX gene (gamma-glutamyl carboxylase), encoding an enzyme important for g-carboxylation of gla-proteins, harbored mutations in six out of seven patients analyzed. These findings all support the hypothesis that the disorder indeed represents a separate clinical and genetic entity, the molecular background of which remains to be unraveled.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
GAMMA-GLUTAMYL CARBOXYLASE, IX PROPEPTIDE, TRANSPORTER, DISORDERS, MATRIX GLA PROTEIN, ABCC6 MUTATIONS, K EPOXIDE-REDUCTASE, SMOOTH-MUSCLE-CELLS, PROPEPTIDE BINDING-SITE, DEPENDENT CLOTTING FACTORS
journal title
JOURNAL OF INVESTIGATIVE DERMATOLOGY
J. Invest. Dermatol.
volume
127
issue
3
pages
581 - 587
Web of Science type
Article
Web of Science id
000244486900014
JCR category
DERMATOLOGY
JCR impact factor
4.829 (2007)
JCR rank
1/41 (2007)
JCR quartile
1 (2007)
ISSN
0022-202X
DOI
10.1038/sj.jid.5700610
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
358828
handle
http://hdl.handle.net/1854/LU-358828
date created
2007-03-29 12:46:00
date last changed
2015-06-17 10:40:06
@article{358828,
  abstract     = {Data on six patients with a Pseudoxanthoma Elasticum (PXE)-like phenotype, characterized by excessive skin folding (resembling cutis laxa) and a deficiency of the vitamin K-dependent clotting factors (II, VII, IX, and X) are presented. A comparison is made between the clinical, ultrastructural, and molecular findings in these patients and those seen in classic PXE and cutis laxa, respectively. Clinical overlap with PXE is obvious from the skin manifestations of yellowish papules or leathery plaques with dot-like depressions at presentation, angioid streaks and/or ocular peau d'orange, and fragmentation and calcification of elastic fibers in the dermis. Important phenotypic differences with PXE include much more severe skin laxity with spreading toward the trunk and limbs with thick, leathery skin folds rather than confinement to flexural areas, and no decrease in visual acuity. Moreover, detailed electron microscopic analyses revealed that alterations of elastic fibers as well as their mineralization were slightly different from those in classic PXE. Molecular analysis revealed neither causal mutations in the ABCC6 gene (ATP-binding cassette subfamily C member 6), which is responsible for PXE, nor in VKORC1 (vitamin K 2,3 epoxide reductase), known to be involved in vitamin K-dependent factor deficiency. However, the GGCX gene (gamma-glutamyl carboxylase), encoding an enzyme important for g-carboxylation of gla-proteins, harbored mutations in six out of seven patients analyzed. These findings all support the hypothesis that the disorder indeed represents a separate clinical and genetic entity, the molecular background of which remains to be unraveled.},
  author       = {Vanakker, Olivier and Martin, Ludovic and Gheduzzi, Dealba and Leroy, Bart and Loeys, Bart and Guerci, Veronica I and Matthys, Dirk and Terry, Sharon F and Coucke, Paul and Pasquali-Ronchetti, Ivonne and De Paepe, Anne},
  issn         = {0022-202X},
  journal      = {JOURNAL OF INVESTIGATIVE DERMATOLOGY},
  keyword      = {GAMMA-GLUTAMYL CARBOXYLASE,IX PROPEPTIDE,TRANSPORTER,DISORDERS,MATRIX GLA PROTEIN,ABCC6 MUTATIONS,K EPOXIDE-REDUCTASE,SMOOTH-MUSCLE-CELLS,PROPEPTIDE BINDING-SITE,DEPENDENT CLOTTING FACTORS},
  language     = {eng},
  number       = {3},
  pages        = {581--587},
  title        = {Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity},
  url          = {http://dx.doi.org/10.1038/sj.jid.5700610},
  volume       = {127},
  year         = {2007},
}

Chicago
Vanakker, Olivier, Ludovic Martin, Dealba Gheduzzi, Bart Leroy, Bart Loeys, Veronica I Guerci, Dirk Matthys, et al. 2007. “Pseudoxanthoma Elasticum-like Phenotype with Cutis Laxa and Multiple Coagulation Factor Deficiency Represents a Separate Genetic Entity.” Journal of Investigative Dermatology 127 (3): 581–587.
APA
Vanakker, O., Martin, L., Gheduzzi, D., Leroy, B., Loeys, B., Guerci, V. I., Matthys, D., et al. (2007). Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 127(3), 581–587.
Vancouver
1.
Vanakker O, Martin L, Gheduzzi D, Leroy B, Loeys B, Guerci VI, et al. Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity. JOURNAL OF INVESTIGATIVE DERMATOLOGY. 2007;127(3):581–7.
MLA
Vanakker, Olivier, Ludovic Martin, Dealba Gheduzzi, et al. “Pseudoxanthoma Elasticum-like Phenotype with Cutis Laxa and Multiple Coagulation Factor Deficiency Represents a Separate Genetic Entity.” JOURNAL OF INVESTIGATIVE DERMATOLOGY 127.3 (2007): 581–587. Print.