Tell me all about Type 1 Collagen, and the COL1A1 gene?

August 10, 2023 5:02 AM

Recent tests have shown that I have a variation of unknown significance on the COL1A1 gene. I'm looking for more information on what this could mean, including information about Type 1 collagen, and specifically collagen, type I, alpha 1. (YANMD, YANMClinicalGeneticist.) Books, research articles, webpages, podcasts, etc - all welcome.

I have a fair grasp of the basics on collagen, Type 1 collagen, and the function of collagen, type I, alpha 1 in making Type 1 collagen.

I've done a dive into relevant scientific literature, and NIH webpages, but am struggling to piece together what the available information means for my specific case, or what factors I should/could bear in mind from this. And I'd welcome a MeFite recap on the basics too, to really cement the knowledge!

Relevant information: I have an ascending aortic dilation, fibromyalgia, Raynaud's, and a host of soft-tissue diseases, alongside lowered immune response.

I am aware that a variant of unknown significance (VUS) means exactly that - it's not known right now what the impact is/could be. But I'm trying to understand what the impact could be, and find out potential sources for further information, as and when the research progresses.

Bonus: what labs are doing research on VUS on COL1A1 right now? It would be good to reach out to the relevant scientists to see if they might discuss my case.

posted by anonymous to Science & Nature (5 answers total)

IANAD/G, I have a genetic disorder but not a COL1A1 mutation. Type I is by far the most common type of collagen in our bodies, and it helps make up skin, bones, and connective tissues. A lot of people with connective tissue disorders have a mutation on COL1A1. It’s also a common mutation for people with osteogenesis imperfecta. If you’re looking for studies of the gene, it might help to look at labs doing research on those types of conditions.

As you said, though VUS means not only that they don’t know what the significance is, but also that they don’t know if it is significant. The majority of VUS are eventually classified as benign (normal genetic variation in the population). The advice I received from a genetic counselor was to proceed as if any VUS was not at all significant.
posted by assenav at 7:48 AM on August 10, 2023 [3 favorites]

It's a firehose of information with not a lot of context, but you might find it interesting to look at ClinVar for all (well, probably not ALL) the different documented variants of COL1A1. You will see that many are known to be pathogenic, and many are known to be benign (e.g. they are fairly common in the population and/or the proteins produced are indistinguishable from the "normal" protein).

The majority of the known the pathogenic variations cause osteogenesis imperfecta and/or are incompatible with life, so that type of variation is not likely to be relevant to you (I assume you would have mentioned osteogenesis imperfecta and since you're posting here I think we can safely say that your variant is not perinatal lethal).

Zooming out a little to the "what *could* the significance be?" There are a lot of different ways a gene can "go wrong" - a simple substitution is generally less disruptive than a deletion or addition that causes a "frame shift" which can be much more serious - imagine if all the word breaks in a sentence were suddenly off by one, like this: "maginei fa llt hew ordb reaksw eres uddenlyo ffb yo ne", as opposed to if you just substituted a few letters: "you juzt sabstituted a few ledders" in which case the sentence remains basically readable and maybe even is still pronounced the same. Your variant could be basically a tiny style guide difference - the equivalent of The New Yorker using diaereses in words like "coöperation." Or it could be an actual misspelling.
posted by mskyle at 8:25 AM on August 10, 2023 [5 favorites]

That's a nice metaphor for mutation types mskyle.
Could use PubMed the database of biomed publications to track down the relevant labs. Such a query: yields one out of Croatia; two fromColumbia NYC papers. A less specific search gives nine leads.
posted by BobTheScientist at 8:53 AM on August 10, 2023

My first recommendation is to work with a genetics specialist in cardiovascular or collagen genetics, if you are not already doing so.

My second would be to do a family study to see if this VUS is in other affected/unaffected family members. This would help classify it as well as give more info for other family members who may need/not need follow-up care.

Third, there are numerous patient organizations for COL1A1-related disorders however most are centered around a specific dx (OI, EHD, etc). Maybe start with the Ehlers-Danlos Society and their recommended Centers of Excellence (if not already part of my first rec).
posted by beaning at 10:11 AM on August 10, 2023 [1 favorite]

Worldwide, there are registries of clinical trials where researchers must register a trial prior to start (typically this is required in order to later publish the results).

Here is the US one: https://clinicaltrials.gov/.
Europe: https://www.clinicaltrialsregister.eu/
Australia/New Zealand: https://www.anzctr.org.au/

You could search these for your specific gene or other terms (Type 1 collagen, for example) to see who is working in this area/what research is happening on these topics.

The WHO International Clinical Trials Registry Platform includes the 3 registries listed above, plus a host of other ones. It also has some helpful info about trials, why register, etc.
posted by lulu68 at 6:24 PM on August 11, 2023