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Updated: Jan 6, 2026

An Improved Method for the Preparation of Type I Collagen From Skin
Published on: January 21, 2014
Absence of Collagen Flowers on Electron Microscopy and Identification of (Likely) Pathogenic COL5A1 Variants in Two
Chloe Angwin1, Angela F Brady2, Marina Colombi3
1National Complex Ehlers-Danlos Syndrome Service London, North West Health Care NHS Trust, Harrow HA1 3UJ, UK. chloeangwin@nhs.net.
Abstract:
Two probands are reported with pathogenic and likely pathogenic COL5A1 variants (frameshift and splice site) in whom no collagen flowers have been identified with transmission electron microscopy (TEM). One proband fulfils the clinical criteria for classical Ehlers-Danlos syndrome (cEDS) while the other does not and presents with a vascular complication. This case report highlights the significant intrafamilial variability within the cEDS phenotype and demonstrates that patients with pathogenic COL5A1 variants can have an absence of collagen flowers on TEM skin biopsy analysis. This has not been previously reported in the literature and is important when evaluating the significance of a TEM result in patients with clinically suspected cEDS and underscores the relevance of molecular analysis.
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