Cookies

Like most websites The Pathologist uses cookies. In order to deliver a personalized, responsive service and to improve the site, we remember and store information about how you use it. Learn more.
Subscribe to Newsletter
Diagnostics Biochemistry and molecular biology, Genetics and epigenetics

Unwinding Collagen’s Complexity

Credit: Nevit Dilmen (CC BY-SA 3.0).

Although there are 13 known types of Ehlers-Danlos syndrome (EDS), a congenital disorder of the connective tissue, definitive diagnosis remains elusive in many cases. Why? With hundreds of potential causative mutations in genes of the collagen and supporting structures, not every patient displays a known pathogenic mutation on panel testing – even when clinical criteria for EDS are met.

In a new study of classical EDS (cEDS), one of the most common types, researchers sequenced genomic DNA from 59 Polish patients (1). Analysis of 35 connective tissue-related genes via next-generation sequencing (NGS) revealed 20 patients with molecular changes in the COL5A1 gene (seven pathogenic or likely pathogenic; 12 benign or likely benign; one unknown), one with COL5A2 changes (likely pathogenic), three with COL1A1 changes (two likely pathogenic; one benign), and six with COL1A2 changes (all unknown). All four genes are known to be related to cEDS. The remaining 29 patients showed no molecular changes in the genes interrogated – further testament to the condition’s phenotypic and genotypic complexity.

It’s clear that, between the disorder’s genetic variability and its overlap with other connective tissue disorders, diagnosis presents a challenge and single-gene testing is often unable to offer conclusive answers. Not only do many patients who meet clinical diagnostic criteria for cEDS exhibit no detectable pathogenic mutations, but others who do possess such mutations may not display a phenotype that meets clinical criteria. Joint hypermobility, skin extensibility, and abnormal scarring – three key diagnostic criteria for cEDS – are often present in other types of EDS and in other connective tissue disorders, muddying the waters when attempting to establish the cause of a patient’s complaints. The authors point to their study as evidence that not all causative genes for EDS have yet been elucidated – and suggest that NGS in combination with panel testing can offer diagnostic support in complex cases.

Receive content, products, events as well as relevant industry updates from The Pathologist and its sponsors.
Stay up to date with our other newsletters and sponsors information, tailored specifically to the fields you are interested in

When you click “Subscribe” we will email you a link, which you must click to verify the email address above and activate your subscription. If you do not receive this email, please contact us at [email protected].
If you wish to unsubscribe, you can update your preferences at any point.

  1. A Junkiert-Czarnecka et al., Curr Issues Mol Biol, 44, 1472 (2022). PMID: 35723357.
About the Author
Michael Schubert

While obtaining degrees in biology from the University of Alberta and biochemistry from Penn State College of Medicine, I worked as a freelance science and medical writer. I was able to hone my skills in research, presentation and scientific writing by assembling grants and journal articles, speaking at international conferences, and consulting on topics ranging from medical education to comic book science. As much as I’ve enjoyed designing new bacteria and plausible superheroes, though, I’m more pleased than ever to be at Texere, using my writing and editing skills to create great content for a professional audience.

Register to The Pathologist

Register to access our FREE online portfolio, request the magazine in print and manage your preferences.

You will benefit from:
  • Unlimited access to ALL articles
  • News, interviews & opinions from leading industry experts
  • Receive print (and PDF) copies of The Pathologist magazine

Register