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Is ME due to Ehlers-Danlos Syndrome "stretchy veins"

Allyson

Senior Member
Messages
1,684
Location
Australia, Melbourne
I just have a question, Allyson, and I am by no means starting anything here; but you have EDS. So, why are you on here? Do you have CFS, too? Isn't the symptomology similar and why be on PR? You know many on here are going to stick to having CFS. They have had it for years. Everyone believes they have what they have. So many here are going to debunk EDS just for that reason on here. It may not resonate with them.

It might really bother them because they feel that they know what they have already. Clearly, not everyone will have EDS. I respect your bringing it to the surface. It's something to look into.

I completely think it's a good idea to keep searching with this thing. One never knows. Especially if they are so so sick. Keep looking and hoping and take breaks from anything health related, if at all possible, too. It's so exhausting.


Hi Spitfire and thanks for the query

yes i have had "cfs " for 25 years
I got diagnosed about 3 years ago afer 20 odd year of being told there was nothing wrong iwth me by a myriad of cdoctors after one a 10 minute session and one blood test max each time.

SO i finally got a diagnosis after doing my own research on the internet , going to my GP with it and saying I am sure i have this - please refer me to this specialist to investigate it

it was then confirmed by 2 separate "cfs" specialists.

So i think i have earned my ME/cfs stripes and have every right to be on this forum.

I had read Dar Teitlbaums book and was confident then tht there was lots of treatment that was going to help me once i got the diagnosis - alas nothing much really did.

So i kept looking.....hence this thread.

more soon as i am tired sorry

Ally
 

Allyson

Senior Member
Messages
1,684
Location
Australia, Melbourne
You know many on here are going to stick to having CFS. They have had it for years. Everyone believes they have what they have. So many here are going to debunk EDS just for that reason on here. It may not resonate with them.

It might really bother them because they feel that they know what they have already. Clearly, not everyone will have EDS. I respect your bringing it to the surface. It's something to look into.

I completely think it's a good idea to keep searching with this thing. One never knows. Especially if they are so so sick. Keep looking and hoping and take breaks from anything health related, if at all possible, too. It's so exhausting.

Hi agian Spitfire

yes this is something that puzzles me too

ME/ CFS is not really an answer for any one - more of a question and a bunch of symptoms that overlap with a lot of other illnesses and have to satifalctory exlanation or cure.

Peope may have "had it for years " but no one is really happy with it as an expalnation so i ma puzled too as to why they feel the need to debunk EDS as a possile alterntive diagnosis without examinning it first.

I ws hoping to examine it in this thread but instead found myself in the positio of defending it...

I suppose we have all been to a doctor who says we do NOT have CFS- how does that feel?

and why do you then believe the doc who says you DO have it and dismiss the negative diagnosis?

and then say you do have ME/cfs when you could believe the other doc and say that you do NOT have it - you are still stuck wth the same set of symptoms either way.

- that is a personal choice to have a disease with a name to it I think, as that is more manageable or graspable than a vague collection ogf mystery symptoms that seem to have no pattern.

For me - I now have an EDS diagnosisas well - EDS is a disease which actually logically explains almost ALL of the symptoms, as i think i have exlained in the thread above - and that is why I think it is a valid theory to examine.

I am not hyermbile at all BTW and also have super tight muscles - esp the thight muscles too

EDs affect iffernt people differntly as the collagn is the builkdign block - if htat is fulty othr things will be too
I am guessigth muscle tightness may be as muscle faxcia is connective tissue and is faulty - and thi sam be why massage helps....totally guessing here.

But from you pic your fingers look like them might be hyperflexible - is that the case?

More soon


Ally
 
Messages
15,786
Peope may have "had it for years " but no one is really happy with it as an expalnation so i ma puzled too as to why they feel the need to debunk EDS as a possile alterntive diagnosis without examinning it first.
No one's denying that some really stupid doctors (and we do know that a fair few exist) might miss EDS. What's been debunked is that suggestion EDS is the same of ME/CFS, or that EDS can be entirely responsible for causing ME/CFS. The major symptoms, the onset, and the biomarkers are completely different.
 

Misfit Toy

Senior Member
Messages
4,178
Location
USA
No, they are not hyper flexible at all. Nothing is. I saw my doc today and he treats or sees many with EDS. He says for sure, I don't have it. I am not sure I want to head to a geneticist. It's a ways away, stressful and expensive.

I think that's why so many on here don't really like new diagnoses coming into the forum sometimes. It's something else to think about, travel to and possibly not have it. Plus, for EDS there is no cure or treatment it seems. It seems like another illness with no end and for many, like myself, that's a hard one. I admit that.

It could explain things but it won't make it any easier than having CFS. Maybe for docs. They will believe in it. The name alone means nothing to me. I want an answer for a better quality of life.

When I was diagnosed with endometriosis, I was so excited...a diagnosis, but there was no cure and my answer at the time was a hysterectomy at age 24. Didn't do it. After awhile, it meant nothing to me that I had a diagnosis that was legit because I was suicidal at one point from the pain.
 

VeganMonkey

Senior Member
Messages
130
Location
Australia
I think that's why so many on here don't really like new diagnoses coming into the forum sometimes. It's something else to think about, travel to and possibly not have it. Plus, for EDS there is no cure or treatment it seems. It seems like another illness with no end and for many, like myself, that's a hard one. I admit that.
.


Yes I totally understand that, it was the same for me, years ago some people on another forum suggested I got checked for POTS/OI and EDS and I was thinking 'no please, not again hospitals, doctors etc' and also that I couldn't have that because I don't have all the symptoms and indeed, no cure, so I thought 'what's the use of it anyway'. So I just let it be. Same as after my CFS diagnosis, I just let it be, there was nothing that could be done after I had tried several different treatments and been in and out of hospitals (and had rather disgusting/painful tests done on me) I was just hospital-tired if that makes sense. And I still am sick of it (no pun intended)

But recently I started reading up on it again and also things have changed a bit because I got many more diagnosis now, thankfully to my ME/CFS specialists, one being POTS and that rang a bell from the past (plus every now and then I get an email from an EDS forum I totally forgot about) and just thought to give it a go.

It's not a big deal now: just a heart ultrasound tomorrow morning (early, yuk!) and then an appointment with the specialist. My CFS/ME specialist sent me there. If I get diagnosed as EDS I know I won't be cured, BUT it will explain why I have POTS, why I got the CFS/ME symptoms (or maybe I just got that as well, who knows), fibromyalgia, IBS and why my eyes are deteriorating (and lots more issues, but that will get boring) Plus a major thing: I had a transplant planned this year, would I have done that without knowing if I have EDS it could go horribly wrong! If I happen to have EDS it can go right if the doctors know what they are dealing with :)

So for me it would be very useful in regard of the transplant and also prevention of injury, and other things I can do to make my life a bit better :)

So don't dismiss it, it's not like other hospital tests and things that are horrible and make you super ill.

I keep reading about new theories, ideas etc and I am reluctant, but after being ill most of my life I feel I want to get pro-active and I owe to my loved ones as well as to myself.
 

ahimsa

ahimsa_pdx on twitter
Messages
1,921
No one's denying that some really stupid doctors (and we do know that a fair few exist) might miss EDS. What's been debunked is that suggestion EDS is the same of ME/CFS, or that EDS can be entirely responsible for causing ME/CFS. The major symptoms, the onset, and the biomarkers are completely different.
I completely agree. No one is denying that EDS exists. No one is denying that EDS may be an alternative diagnosis in some cases (ME diagnosis was a mistake). No one is denying that EDS may be an additional diagnosis in some cases (ME patients can have more than one diagnosis).

The main point that is being disputed is the statement that EDS causes all cases of ME (or ME/CFS, or CFS). That statement seems to be overly simplistic.

I don't know any research studies that support a causal link between EDS and ME. I've read a few of the lists of diagnostic criteria for different types of EDS and none of them match up with the diagnostic criteria for ME (see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427890/ -or- http://sacfs.asn.au/download/me_international_consensus_primer_for_medical_practitioners.pdf )

Who knows, maybe future scientific studies will go in that direction, but the evidence that we have now does not point to the fact that EDS is the primary cause for most cases of ME.

TheSpitfire said:
I think that's why so many on here don't really like new diagnoses coming into the forum sometimes. It's something else to think about, travel to and possibly not have it.
I can't speak for others but I am not trying to reject a new diagnosis. Far from it! I am happy to learn about EDS. I'm reading about it so that I can figure out whether it applies to me. Sure, no one wants yet another diagnosis. But ignorance of the diagnosis is not going to keep it from being true.

(By the way, TheSpitfire, I'm another patient with an endometriosis diagnosis so I already have multiple diagnoses. :( It would be pretty silly to ignore more diagnoses when I already have a bunch. And yes, endometriosis pain is horrible. I was in agony and can relate to wanting to end it all. Surgical excision of the endometriosis tissue by an endo expert, not a hysterectomy, is what finally helped relieve my endo pain. That said, this surgery does not work for everyone, but it's too bad that some doctors tell patients that full hysterectomy is the only answer when there are other surgical options.)

In fact, I'm fascinated by the overlap between different types of Orthostatic Intolerance and EDS, for example. I've had a diagnosis of NMH (Neurally Mediated Hypotension, aka, NCS and other names) since 1995. I'm interested in all the different types of OI or autonomic dysfunction and what causes them. I would definitely like to learn more about EDS so that I can figure out whether it is part of my problem. I hope to go to a specialist to figure that out one day. (but I have to pace myself as far as money and energy so it might be a while before that happens.)

So, I don't think the problem on this thread is resistance to or denial of an EDS diagnosis. I think the problem on this thread is trying oversimplify things and give simple answers to complex problems. Remember that old saying,
For every complex problem there is an answer that is clear, simple, and wrong.
- H. L. Mencken

I do agree with the idea that what is useful for most patients is not the name of the diagnosis but whether there are any treatment options or a cure. For example, a diagnosis of either ME or CFS has given me zero helpful treatments over the years. But my 1995 diagnosis of Neurally Mediated Hypotension (a type of OI) has provided quite a few treatments (midodrine, florinef, extra salt/potassium, increased water intake, etc.) as well as the understanding of what types of things are likely to trigger my symptoms (e.g., heat, standing, sitting upright, etc.).

So I understand that most patients want a treatment or cure, not a name.
 

Sushi

Moderation Resource Albuquerque
Messages
19,935
Location
Albuquerque
...So, I don't think the problem on this thread is resistance to or denial of an EDS diagnosis. I think the problem on this thread is trying oversimplify things and give simple answers to complex problems. Remember that old saying, For every complex problem there is an answer that is clear, simple, and wrong.
- H. L. Mencken

I do agree with the idea that what is useful for most patients is not the name of the diagnosis but whether there treatment options or a cure. For example, a diagnosis of either ME or CFS has given me zero helpful treatments over the years. But my 1995 diagnosis of Neurally Mediated Hypotension (a type of OI) has provided quite a few treatments (midodrine, florinef, extra salt/potassium, increased water intake, etc.) as well as the understanding of what types of things are likely to trigger my symptoms (e.g., heat, standing, sitting upright, etc.).

So I understand that most patients want a treatment or cure, not a name.

I am also looking for treatment options as well as getting accurately diagnosed. But have been more lucky with the ME diagnosis--I have been prescribed treatments that have really helped me. On the other hand, while I also have EDS, I have not found any treatment for it specifically. Rather I have learned precautions to take and remedial measures to take like seeing an osteopath regularly. So, as far as treatment, at the moment I am focused on ME.

Best,
Sushi
 

ahimsa

ahimsa_pdx on twitter
Messages
1,921
I am also looking for treatment options as well as getting accurately diagnosed. But have been more lucky with the ME diagnosis--I have been prescribed treatments that have really helped me.

Sushi, I absolutely believe that it's possible to treat patients based on an ME diagnosis. I hope my message did not come across the wrong way!

I think treatment for ME or CFS works when the patient finds a good doctor with the right expertise who can do the right tests and so on. My problem is that I have not been able to find an actual ME or CFS specialist in my area. So my local docs have no clue and that's why the ME/CFS diagnosis has been useless for me as far as treatment.

I think that there might be some treatments that would help me. But when going to an ME specialist involves travel then it's hard to commit to the money, energy and time to do that. I've seen some successes but also a lot of failures when it comes to patients who go long distances to get treatment for ME. Maybe one day I will consider it but for now I'm not sure I'm up to long travel for ME treatment.
 

VeganMonkey

Senior Member
Messages
130
Location
Australia
I'm being treated with something that works for CFS, POTS and EDS and it works for me, my specialists say it helps counter effect the oxidation process that people with ME/CFS have. Not sure what it does for EDS, or how it works with POTS but I have read that EDS patients get this treatment too. They are B12 injections. They make me recover faster. After having been out of the house I normally need 3 days sleep but now I can actually do things. Not like a normal person, but a bit more than I normally would, plus less sleep is needed.
So treatment-wise I'm quite happy! And I am happy I have more diagnosis now than in the last when I had nothing at all. I know it's frustrating when you have a diagnosis but not cure, but at least you know what you have.

Btw had my heart ultrasound today. Will know more about that in two weeks time.


VeganMonkey, a transplant? That sounds awful! I am not sure what kind of transplant, but I am so sorry!

It's not as horrible as it sounds but horrible enough for me. I need a cornea transplant. If the new one wouldn't adhere well I would go blind in that eye. So that's why I want to research everything possible before getting it done. I already can't use that eye (that's why it's needed) and it makes that I easily get accidents (I broke my back last year due to bad eye sight), I can't drive a car and just don't want to break my back again of course haha.
 

ahimsa

ahimsa_pdx on twitter
Messages
1,921
I'm being treated with something that works for CFS, POTS and EDS and it works for me, my specialists say it helps counter effect the oxidation process that people with ME/CFS have. Not sure what it does for EDS, or how it works with POTS but I have read that EDS patients get this treatment too. They are B12 injections. They make me recover faster.
I have heard that B-12 injections can help some patients. I'm so glad that they work for you!

I took these shots for about 2 years during those years when I was first sick, sometime in the early to mid-1990s. I was seeing a Naturopathic doctor in addition to all the various MDs and specialists. So I was trying a lot of different things. These shots seemed like a harmless option (no side effects) but I don't think they did much for me.

My blood levels of B-12 did indeed go way up (I remember an MD being very curious about my high levels until I told him I was getting these shots). And I was advised to keep doing them for at least a year to see whether they helped. The only noticeable difference for me was that perhaps they reduced my muscle twitches (fasiculations). But they did not give me more energy or help me recover from crashes faster or anything like that.

So perhaps my situation is somehow different from the ME or CFS patients who get help from B-12 shots? Or maybe it was a different form of B-12? I have no idea but I'm glad it's working for you.

VeganMonkey, sending you some :hug: hugs :hug: and the very best of luck for your heart ultrasound and also your upcoming cornea transplant.
 

Allyson

Senior Member
Messages
1,684
Location
Australia, Melbourne
Yes I totally understand that, it was the same for me, years ago some people on another forum suggested I got checked for POTS/OI and EDS and I was thinking 'no please, not again hospitals, doctors etc' and also that I couldn't have that because I don't have all the symptoms and indeed, no cure, so I thought 'what's the use of it anyway'. So I just let it be. Same as after my CFS diagnosis, I just let it be, there was nothing that could be done after I had tried several different treatments and been in and out of hospitals (and had rather disgusting/painful tests done on me) I was just hospital-tired if that makes sense. And I still am sick of it (no pun intended)

But recently I started reading up on it again and also things have changed a bit because I got many more diagnosis now, thankfully to my ME/CFS specialists, one being POTS and that rang a bell from the past (plus every now and then I get an email from an EDS forum I totally forgot about) and just thought to give it a go.

It's not a big deal now: just a heart ultrasound tomorrow morning (early, yuk!) and then an appointment with the specialist. My CFS/ME specialist sent me there. If I get diagnosed as EDS I know I won't be cured, BUT it will explain why I have POTS, why I got the CFS/ME symptoms (or maybe I just got that as well, who knows), fibromyalgia, IBS and why my eyes are deteriorating (and lots more issues, but that will get boring) Plus a major thing: I had a transplant planned this year, would I have done that without knowing if I have EDS it could go horribly wrong! If I happen to have EDS it can go right if the doctors know what they are dealing with :)

So for me it would be very useful in regard of the transplant and also prevention of injury, and other things I can do to make my life a bit better :)

So don't dismiss it, it's not like other hospital tests and things that are horrible and make you super ill.

I keep reading about new theories, ideas etc and I am reluctant, but after being ill most of my life I feel I want to get pro-active and I owe to my loved ones as well as to myself.

yes my sympathies too Vegan monkey and yes you would be at increased risk of bleeding in an surgery ( my sister had a PPH after her socond baby) and for dental EDSers need more local anaesthetic - not sure if that applies to general surgery too.

I alwyas try to schedule anythig fot he latest possible time. Wa not possible at Genetic CTD cliic as the lates time was 11am but if i can i do - even if it meamns ogoing a later day as often i need to cancel the later time.

best


A
 

Allyson

Senior Member
Messages
1,684
Location
Australia, Melbourne
I have heard that B-12 injections can help some patients. I'm so glad that they work for you!

I took these shots for about 2 years during those years when I was first sick, sometime in the early to mid-1990s. I was seeing a Naturopathic doctor in addition to all the various MDs and specialists. So I was trying a lot of different things. These shots seemed like a harmless option (no side effects) but I don't think they did much for me.

My blood levels of B-12 did indeed go way up (I remember an MD being very curious about my high levels until I told him I was getting these shots). And I was advised to keep doing them for at least a year to see whether they helped. The only noticeable difference for me was that perhaps they reduced my muscle twitches (fasiculations). But they did not give me more energy or help me recover from crashes faster or anything like that.

So perhaps my situation is somehow different from the ME or CFS patients who get help from B-12 shots? Or maybe it was a different form of B-12? I have no idea but I'm glad it's working for you.

VeganMonkey, sending you some :hug: hugs :hug: and the very best of luck for your heart ultrasound and also your upcoming cornea transplant.



HI Ahimsa _

IM B 12 help me sleep better - that is the only effect i have noticed but i am vey glad of that so stick with them. Oral/sublngual B 12 i took for many years prior to the IM ad it did nothing at all for me .

My geneticist tells me it with Vitamin C is the vital element for building connective tissue - along with glucosaminoglycans and chondriatin. i have been taking them too therefore for 3 weeks now and they are futher improving my sleep ! ......again it is worth it just for that.


best

Ally
 

Allyson

Senior Member
Messages
1,684
Location
Australia, Melbourne
I'm being treated with something that works for CFS, POTS and EDS and it works for me, my specialists say it helps counter effect the oxidation process that people with ME/CFS have. Not sure what it does for EDS, or how it works with POTS but I have read that EDS patients get this treatment too. They are B12 injections. They make me recover faster. After having been out of the house I normally need 3 days sleep but now I can actually do things. Not like a normal person, but a bit more than I normally would, plus less sleep is needed.
So treatment-wise I'm quite happy! And I am happy I have more diagnosis now than in the last when I had nothing at all. I know it's frustrating when you have a diagnosis but not cure, but at least you know what you have.

Btw had my heart ultrasound today. Will know more about that in two weeks time.




It's not as horrible as it sounds but horrible enough for me. I need a cornea transplant. If the new one wouldn't adhere well I would go blind in that eye. So that's why I want to research everything possible before getting it done. I already can't use that eye (that's why it's needed) and it makes that I easily get accidents (I broke my back last year due to bad eye sight), I can't drive a car and just don't want to break my back again of course haha.

Hope it goes well VM, and yes corneal problems are ultra typical of EDS - another reason why it was worth you getting a diagnosis - or indeed any of us - to know what to look out for - eg the aortic arch weakness problems that can be detected on cardiac ultrasound whichi is why I assume you had one done.

Hope the results are good for you - mine was clear and i do not need to be re- tested now for 5 years.
They are recommmended now for ALL types of EDS not just the vascular type as once thought.

best

Ally
 

Allyson

Senior Member
Messages
1,684
Location
Australia, Melbourne
2013 Mar;19(2):246-50. doi: 10.1111/hae.12020. Epub 2012 Oct 3.

Suspected collagen disorders in the bleeding disorder clinic: a case-control study.

Jackson SC, Odiaman L, Card RT, van der Bom JG, Poon MC.
Source

Division of Hematology, Department of Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada. sjackson@providencehematology.com

... Abstract
Disorders of collagen are associated with a mild bleeding tendency because of the potential abnormal interaction of collagen, von Willebrand factor (VWF) and platelets required during primary haemostasis and due to generalized soft tissue fragility. Abnormal collagen may contribute to bleeding in existing mucocutaneous bleeding disorders, but the prevalence in this setting is unknown.

Generalized symptomatic joint hypermobility (SJH) is common in collagen disorders and may be objectively measured. To assess the association between symptomatic joint hypermobility and mucocutaneous bleeding disorders, we performed a case-control study in which case subjects were 55 consecutive individuals who had visited our bleeding disorder clinic with a diagnosis of von Willebrand disease, low von Willebrand factor levels, mild platelet function disorder or undefined bleeding disorder. Controls were 50 subjects without a bleeding disorder, and were age and gender matched to the cases. All subjects were assessed with: (i) Beighton score for joint hypermobility, (ii) revised Brighton criteria, (iii) Condensed MCMDM1-VWD bleeding questionnaire, and (iv) haemostasis laboratory studies. The prevalence of SJH/suspected collagen disorder in the bleeding disorder clinic was 24% (13/55) compared with 2% (1/50) in the control population (OR 15, 95% CI 2-121).

Seventy-seven per cent of bleeding disorder clinic SJH subjects (10/13) had a prior personal or family history of Ehlers-Danlos, Benign Joint Hypermobility Syndrome or Osteogenesis Imperfecta (OI). Symptomatic joint hypermobility was associated with increased odds of an underlying mucocutaneous bleeding disorder. These findings suggest that a collagen disorder is common and often unrecognized in the bleeding disorder clinic as a potential contributor to the bleeding symptoms.



Thanks Janet
 

Allyson

Senior Member
Messages
1,684
Location
Australia, Melbourne
2013 Feb 27. [Epub ahead of print]

Next-generation sequencing for disorders of low and high bone mineral density.

Sule G, Campeau PM, Zhang VW, Nagamani SC, Dawson BC, Grover M, Bacino CA, Sutton VR, Brunetti-Pierri N, Lu JT, Lemire E, Gibbs RA, Cohn DH, Cui H, Wong LJ, Lee BH.

Source

Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, R814, MS225, Houston, TX, 77030, USA.

... Abstract
To achieve an efficient molecular diagnosis of osteogenesis imperfecta (OI), Ehlers-Danlos syndrome (EDS), and osteopetrosis (OPT), we designed a next-generation sequencing (NGS) platform to sequence 34 genes. We validated this platform on known cases and have successfully identified the causative mutation in most patients without a prior molecular diagnosis.

INTRODUCTION:
Osteogenesis imperfecta, Ehlers-Danlos syndrome, and osteopetrosis are collectively common inherited skeletal diseases. Evaluation of subjects with these conditions often includes molecular testing which has important counseling and therapeutic and sometimes legal implications. Since several different genes have been implicated in these conditions, Sanger sequencing of each gene can be a prohibitively expensive and time-consuming way to reach a molecular diagnosis.

METHODS:
In order to circumvent these problems, we have designed and tested a NGS platform that would allow simultaneous sequencing on a single diagnostic platform of different genes implicated in OI, OPT, EDS, and other inherited conditions, leading to low or high bone mineral density. We used a liquid-phase probe library that captures 602 exons (~100 kb) of 34 selected genes and have applied it to test clinical samples from patients with bone disorders.
RESULTS:
NGS of the captured exons by Illumina HiSeq 2000 resulted in an average coverage of over 900X. The platform was successfully validated by identifying mutations in six patients with known mutations. Moreover, in four patients with OI or OPT without a prior molecular diagnosis, the assay was able to detect the causative mutations.

CONCLUSIONS:
In conclusion, our NGS panel provides a fast and accurate method to arrive at a molecular diagnosis in most patients with inherited high or low bone mineral density disorders.

A
 

Allyson

Senior Member
Messages
1,684
Location
Australia, Melbourne
sorry no title or other detais for this abstract - I assume it is recent but wil post details later if i get them

Abstract

Vascular Ehlers-Danlos syndrome (EDS) type IV is the most severe form of EDS. In many cases, the disease is caused by a point mutation of Gly in type III collagen. A slower folding of the collagen helix is a potential cause for overmodifications. However, little is known about the rate of folding of type III collagen in patients with EDS. In order to understand the molecular mechanism of the effect of mutations a system was developed for bacterial production of homotrimeric model polypeptides. The C-terminal quarter, 252 residues, of the natural human type III collagen was attached to (GPP)7 with the type XIX collagen trimerization domain (NC2). The natural collagen domain forms a triple helical structure without 4-hydroxylation of proline at low temperature. At 33 °C, the natura...l collagenous part is denatured, but the C-terminal (GPP)7-NC2 remains intact. Switching to a low temperature triggers the folding of the type III collagen domain in a zipper-like fashion that resembles the natural process. We used this system for the two known EDS mutations (Gly-to-Val) in the middle at G910 and at the C-terminus at G1018. In addition, wild-type and Gly-to-Ala mutants were made. The mutations significantly slow down the overall rate of triple helix formation. The effect of the Gly-to-Val mutation is much more severe compared with Gly-to-Ala. This is the first report on the folding of collagen with EDS mutations, which demonstrates local delays in the triple helix propagation around the mutated residue.


Thanks Janet