Deficiency of tenascin-X causes abnormalities in dermal elastic fiber morphology.
Deficiency of the extracellular matrix protein tenascin-X (TNX) was recently described as the molecular basis of a new, recessive type of Ehlers-Danlos syndrome. Here we report gross abnormalities of the elastic fibers and microfibrils in the dermis of these patients, and reduced dermal collagen content, as determined by quantitative image analysis. The ascending, fine elastic fibers in the papillary dermis were absent or inconspicuous and had few branches. The coarse elastic fibers of the reticular dermis were fragmented and clumped. At the ultrastructural level, irregular and immature elastin fibers and fibers devoid of microfibrils were observed. In TNX-deficient patients the dermal collagen density was reduced, but no structural abnormalities in the collagen fibrils were found. These findings suggest that both elastic fiber abnormalities and reduced collagen content contribute to the observed phenotype in TNX-deficient patients.
Zweers
Manon C
MC
Department of Dermatology, University Medical Center, St Radboud Nijmegen, Nijmegen, The Netherlands. m.zweers@derma.umcn.nl
van Vlijmen-Willems
Ivonne M
IM
van Kuppevelt
Toin H
TH
Mecham
Robert P
RP
Steijlen
Peter M
PM
Bristow
Jim
J
Schalkwijk
Joost
J
D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D020405:Dermis / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D004535:Ehlers-Danlos Syndrome / Q000378:metabolism* / Q000473:pathology*; D004547:Elastic Tissue / Q000473:pathology* / Q000648:ultrastructure; D000071837:Fibrillins; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D008661:Metabolism, Inborn Errors / Q000378:metabolism / Q000473:pathology; D020894:Microfibrils / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D008875:Middle Aged; D019063:Tenascin / Q000172:deficiency*
D000071837:Fibrillins; D008840:Microfilament Proteins; D019063:Tenascin; C081865:tenascin X; D003094:Collagen