Genetic Freak? Or Something Else?

[minton]

Okay so, I'm confused. If celiac is genetic, Why am I the only one in my whole extended family with it? My mom has Ibs but she was tested for Celiac (blood work and an endoscopy) and both were clearly negative. My dad was tested as well. They were even gene tested. I am the only one as far back as great great grandparents (they aren't around to ask but those who remember them said they were of perfect health. Some were even wheat farmers!) There is only one other person in my whole extended family that has a food allergy and thats a very distant cousin that's allergic to milk. His father was allergic to milk too and his father is not genetically related to me. I have a large extended family and it stumps me how I am the only one with celiac. (I might add that any "sickly" family members were tested for celiac themselves after my diagnosis.Their tests varied. None improved on a gluten-free diet either.)

The ONLY guess I have is that my dad was exposed to Agent Orange long before I was born. Supposedly, emerging research indicates that the genetic damage it CAN cause can lead to GI problems in offspring. There is not even sufficient evidence to prove that much and the highest prevelence of any birth defects are from a mother exposed to Agent Orange. Also, I might add that I have 3 other siblings, two of which were born after dad's exposure and all 3 ofthem are in perfect health. So that is VERY unlikely to be the cause.

Am I just a random genetic "freak"? I mean I was tested (endoscopy, blood test, no gene test though). I not only test positive, I showed symptoms from the day I was born (gluten in the breast milk). Does this happen alot where there is only one celiac in the whole family? Any ideas what might have happened in the genes to cause it?

Sidenote: the reason I ask is because I am very interested in genetics and overall medicine studies (will probably go to college to be a doctor of some sort) and I would like to understand what happened.

[lizard00]

What were your parents genetic results?

It is estimated that somewhere around 30% of the US population carry the genetic markers for Celiac, but it is only estimated that around 1% of the US population will actually develop celiac disease. Whether those numbers are accurate or not remains to be seens, BUT could be that whomever passed on the celiac genes is at this point only a carrier, and the disease has not been triggered in them.

OR since your mom is the symptomatic one, she could have it, even with negative tests.

My mom carries at least one copy of the gene, but tests negative and is asymptomatic. So, the assumption is that she doesn't have it. She has had more than her fair share of stress in her life, so I would think that if it were going to be triggered, it would have been by now.

[minton]

My parents didn't actually show me their results, only discussed them with me after a doctor discussed the results with them. They weren't very specific but said they had not shown gene markers. I tried to get more information but that's about all they paid attention to.

[sbj]

If I understand your question, you are wondering why celiac is not passed on more frequently if it is genetic. I think that is because celiac disease is associated with multiple genes and not just one. That is, celiac disease is a polygenic disorder. (If celiac disease was a single gene disorder then it would be far easier to predict one's chances of inheriting it from a parent.) See the following link where the differences between single gene disorders and poygenic disorders are described.

Open Original Shared Link

Celiac disease is a multifactorial and polygenic (complex) disorder. That means that there is no clear-cut pattern of inheritance:

Genetic disorders may also be complex, multifactorial or polygenic, this means that they are likely associated with the effects of multiple genes in combination with lifestyle and environmental factors. Multifactoral disorders include heart disease and diabetes. Although complex disorders often cluster in families,

they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person

[minton]

so sbj in a family my size (extended family is over 200 people, not including those who have passed on that were perfectly healthy), would it make sense that I am the only one?

(I am trying to make sense of what you replied with)

[Jestgar]

Many diseases are a result of both genetics, and what you have experienced (illnesses and such). Many people in your family may have genetic combinations similar to yours, but you are the only one who has eaten the way you do, traveled the way you do, gotten sick the way you do, etc.

[sbj]

so sbj in a family my size (extended family is over 200 people, not including those who have passed on that were perfectly healthy), would it make sense that I am the only one?

(I am trying to make sense of what you replied with)

It is possible that you are the only one for a variety of reasons. Is it likely? I dunno - there is simply too much that is unknown about the genetics of celiac. The first thing we would have to do is get all 200 members tested for the genetic markers. You coud be the only one simply because we don't know everything about how celiac is inherited and why it develops in only some of those who have the genetic markers. In your case there could indeed be some environmental or lifestyle factor in play.

Put it this way, too, there has to be an initial mutation somewhere along the line. Since you might be the first in your family to have celiac, and since celiac appears to be caused by multiple genes not all of which are known, you might be the first to have spontaneously mutated one of the additional unknown genes.

Remember, even in first degree relatives there is only a 1 in 10 chance of them having the genetic markers. (Am I right?) And then, even if that one out of ten has the marker, there is still an even lesser chance that they have symptoms.

I knowe of no one else in my immediate or extended family with celiac disease either.

[minton]

Thank you sbj for explaining further. that does make sense now. Yay now I can at least explain better when a family member asks!

[April in KC]

If you have the HLA-DQ2 or DQ8 serotype, you had to get it from ONE of your natural parents. There is no way around this. However, having HLA-DQ2 does not guarantee that you will develop Celiac Disease - it is just a necessary part, and the other tipping point (environment? stress? other genes?) is not known yet.

So one scenario might go something like this:

Dad has HLA-DQ4 and HLA-DQ6, Mom has HLA-DQ5 and HLA-DQ2 (but no Celiac Disease).

Daughter has HLA-DQ6 and HLA-DQ2 (but does have Celiac Disease).

In this case the Celiac gene was passed from mom, but the mom has not developed the disease - lacking the tipping point (stress/environment/other genes) that causes Celiac Disease to develop.

When you have kids, you will pass ONE of your copies of HLA-DQ to your children. Your spouse will contribute the other copy. Each child stands a chance of receiving your Celiac gene, but also stands a chance of receiving your non-Celiac gene (unless you carry two copies of the Celiac gene, which I will touch on in a second).

In my case, both I and my husband each carry a Celiac gene (and in fact have Celiac disease). Our kids have a much higher chance of getting a Celiac gene...if they don't get it from me, they might get it from their dad. And, in fact, that is what has happened. All three of our boys are gluten-sensitive, and one had a very bad case of Celiac Disease. We haven't had his genes tested, but it seems possible that he is homozygous for HLA-DQ2, meaning he has two copies of the Celiac gene. People with two copies tend to have more risk for complications. Another of our sons has at least a degree of gluten sensitivity (was losing weight to diarhhea at age 3), and we did have him tested, and he carries HLA-DQ2 and HLA-DQ4. Sometimes kids under the age of 5 do not test positive for the blood antibodies. Some adults may not test positive, either - at least it would seem that way from reading this board. I am a fan of having a Celiac panel (4 different antibodies tested) vs. a single TTG test, but it is more costly for providers, and still doesn't offer certainty, so they don't always run the full panel. I had some of the antibodies, but not all of them, and I definitely have Celiac Disease (was losing weight at a rate of 10-15 lbs. per month prior to going gluten free). I was 5'6" and 106 when I finally healed up...if I had gone another month, I would have been in the low 90s for weight.

There are some very good articles about HLA, HLA-DQ, and HLA-DQ2, etc., out on Wikipedia. You have to read and learn the scientific terminology, but it is fascinating.

To your original question about how many family members should be affected, I have seen studies that suggest anywhere from 1 in 17 to 1 in 10. More than that should carry the gene. If you are really curious and want to read summaries of studies, you can go to www.pubmed.com and type in search terms like Celiac, HLA, etc.

Hope that helps a bit.

[ShayFL]

Have every single 200 people been tested with blood/biopsy/genetic tests?

I am one who believes there are plenty of Celiacs out there WITHOUT the 2 U.S. recognized Celiac genes. And I also believe that "gluten intolerance" can be the early signs of Celiac with or without the 2 U.S. recognized genes.

Your Mom may not have Celiac based on U.S. criteria, but she sure might be "gluten intolerant". Has anything totally cleared up her IBS? Has she tried a gluten-free diet?

[ravenwoodglass]

What genes did they test for? There is no way if you are celiac that at least one of your parents wouldn't carry one of the genes. Celiac is a genetic difference not a defect and in addition there is a great deal other than just GI disorders that come from it. It can effect many other organs including brain. How long ago was it that your Mom had the blood test and scope? Both could have been a false negative or the blood test may have been a low postive and she was told it was negative. There are more genes than the recognized DQ2 or DQ8 that are involved in celiac but in the US those are the only genes they currently test for.

[minton]

I doubt I'm adopted (my brother was at my birth haha) but I swear to you, neither of my parents carry the genes according to their doctors. Maybe those who suggested that they carry the other non-US recognized genes might be right. Their doctors aren't as open minded as mine (neither of them have seen my doctor as patients themselves...he's a bit expensive and doesn't accept our insurance)so perhaps they only tested for the US genes. That is definitely a possibility.

As far as I know, all 200 people were not tested. Only about 100 were. As I said above, their tests varied. Some had gene testing, some blood, some biopsy and some had more than one type of testing done. None showed any markers or evidence. Their reasons for testing also varied, some were physically sick, others had mental problems like autism or ADD (my mom told them it may be an underlying cause of their trouble), others had no trouble but their doctors erred on the side of caution and tested. I'd say most of them tried the gluten free diet anyway and reported back to my mom that there was no difference at all after 2-3 months of the diet.

ShayFL, nothing has cleared up my mom's ibs. She has a small problem with self-control especially with food and though she wants to try a gluten free diet, favorite foods will get her off track within 12 hours of starting. It happens everytime. She also tried fiber supplements (they reccomend it to treat ibs apparently) and while she stuck with that for 3 weeks, nothing changed. I don't know what else she has tried although I do know she uses anti-diarheals and laxatives as needed for her symptoms. I would love her to try the gluten-free diet and have offered to cook the foods I eat for her too. I only cook foods that taste extremely close to gluteny since I lived on gluten 17 years and am a bit spoiled by it. It's mainly her lunch breaks at work that ruin her. It's a shame, I'd love to eat the same as someone else for once haha.

ravenwoodglass, My dad and mom have both been tested twice. My mom was tested when I was diagnosed (2.5 years ago) and about a year ago when she had to be hospitalized for GI trouble (turned out it was her gall bladder!). My dad was tested shortly after my diagnosis and about 3 months ago during hospitalization. He had pancreatitis and they did an endoscopy, my mom asked them to test for it while they were in there anyway because his regular daily symptoms kinda fit the odd pain that i had when still eating gluten prior to diagnosis. Their "my diagnosis" tests were genetic and I think blood too (my mom for sure was blood tested). They both had biopsy since then.

While stress is a possibility to have started the celiac process in me, it's not likely given that I had symptoms from birth (was getting glutened by breast milk!). And if either of my parents carried the genes that could be activated by stress, then its a miracle they aren't dying (figuratively speaking) right now...they've raised 5 kids to adulthood (I'm their last to leave the nest) and each kid gave them crazy amounts of stress in different ways.

One other odd question...not sure if it's relevant...when my mom was younger she lived a little ways away from a wheat field. She has never tested allergic to any food including wheat but she has scary stories about how whenever she rode her bike past that wheat field she would break out in hives head to toe and she was so scary looking and swollen that her horror loving brothers were terrified of her and cried when they looked at her. Is it possible that she has a minor allergy (so minor that allergen tests dont show it) to wheat and that i got that gene from her mixed with others from my dad to cause celiac?

[Amber M]

I doubt I'm adopted (my brother was at my birth haha) but I swear to you, neither of my parents carry the genes according to their doctors. Maybe those who suggested that they carry the other non-US recognized genes might be right. Their doctors aren't as open minded as mine (neither of them have seen my doctor as patients themselves...he's a bit expensive and doesn't accept our insurance)so perhaps they only tested for the US genes. That is definitely a possibility.

As far as I know, all 200 people were not tested. Only about 100 were. As I said above, their tests varied. Some had gene testing, some blood, some biopsy and some had more than one type of testing done. None showed any markers or evidence. Their reasons for testing also varied, some were physically sick, others had mental problems like autism or ADD (my mom told them it may be an underlying cause of their trouble), others had no trouble but their doctors erred on the side of caution and tested. I'd say most of them tried the gluten free diet anyway and reported back to my mom that there was no difference at all after 2-3 months of the diet.

ShayFL, nothing has cleared up my mom's ibs. She has a small problem with self-control especially with food and though she wants to try a gluten free diet, favorite foods will get her off track within 12 hours of starting. It happens everytime. She also tried fiber supplements (they reccomend it to treat ibs apparently) and while she stuck with that for 3 weeks, nothing changed. I don't know what else she has tried although I do know she uses anti-diarheals and laxatives as needed for her symptoms. I would love her to try the gluten-free diet and have offered to cook the foods I eat for her too. I only cook foods that taste extremely close to gluteny since I lived on gluten 17 years and am a bit spoiled by it. It's mainly her lunch breaks at work that ruin her. It's a shame, I'd love to eat the same as someone else for once haha.

ravenwoodglass, My dad and mom have both been tested twice. My mom was tested when I was diagnosed (2.5 years ago) and about a year ago when she had to be hospitalized for GI trouble (turned out it was her gall bladder!). My dad was tested shortly after my diagnosis and about 3 months ago during hospitalization. He had pancreatitis and they did an endoscopy, my mom asked them to test for it while they were in there anyway because his regular daily symptoms kinda fit the odd pain that i had when still eating gluten prior to diagnosis. Their "my diagnosis" tests were genetic and I think blood too (my mom for sure was blood tested). They both had biopsy since then.

While stress is a possibility to have started the celiac process in me, it's not likely given that I had symptoms from birth (was getting glutened by breast milk!). And if either of my parents carried the genes that could be activated by stress, then its a miracle they aren't dying (figuratively speaking) right now...they've raised 5 kids to adulthood (I'm their last to leave the nest) and each kid gave them crazy amounts of stress in different ways.

One other odd question...not sure if it's relevant...when my mom was younger she lived a little ways away from a wheat field. She has never tested allergic to any food including wheat but she has scary stories about how whenever she rode her bike past that wheat field she would break out in hives head to toe and she was so scary looking and swollen that her horror loving brothers were terrified of her and cried when they looked at her. Is it possible that she has a minor allergy (so minor that allergen tests dont show it) to wheat and that i got that gene from her mixed with others from my dad to cause celiac?

Very interesting. Your mom must have some kind of "wheat thing" with that story! If you knew exactly what the gene tests were, it would help. Like any DQ genes? In other Countries they do recognize more genes that U.S. I tested negative on blood and biopsy as many others have. My gene test did pick up (listed below on signature) and some doctors believe there is "no problem" if its not specific DQ2 or 8. I am gluten sensitive with Ataxia and lower GI problems. I bet your mom is at least part of the key here. See if you can look at her gene test results. You had to get the gene from one of your parents according to what I have read too.

[neesee]

Could you possibly be HLA-DR5/DR7? In other words, could you have inheritited half a gene from each parent? Open Original Shared Link

neesee

[georgie]

My Mum is going to see her Dr soon. Am I reading the genetics correctly when it says I MUST have one parent with the DQ2 gene - even if they are asymtomatic to Celiac ? It would be interesting to find out if Mum carries the gene. I guess I am just curious...My Dad passed away a few years ago so if Mum tests negative I can assume I inherited the gene from my late father?

[Amber M]

My Mum is going to see her Dr soon. Am I reading the genetics correctly when it says I MUST have one parent with the DQ2 gene - even if they are asymtomatic to Celiac ? It would be interesting to find out if Mum carries the gene. I guess I am just curious...My Dad passed away a few years ago so if Mum tests negative I can assume I inherited the gene from my late father?

Thats the way I understand it on the genes, unless I am wrong. Anyone else?

I was reading your diagnosis list and am wondering if you are completly gluten free? Are you showing signs of improvement in all ways? I have gluten "ataxia", but am geting better slowly.

I am lugume-soy free for years already (although I had minute amounts at times) and now can not tollerate ANY soy at all. So I know how hard it is to be SOY-GLUTEN free! Hey, it could be worse! Others are alot more limited than us.

[georgie]

I was reading your diagnosis list and am wondering if you are completely gluten free?

Absolutely. The whole house is gluten-free and hubbie eats as I do. I was dairy free but now can be lactose free and OK. I am also soy free and fructose light. I started wearing a mask to feed my horses this year which helped. It just seems that I am an autoimmune disaster and possible have PolyGlandular Autoimmune Syndrome Type 2. Drs are still all arguing....

Thats the way I understand it on the genes, unless I am wrong. Anyone else?

Mum is going to Dr tomorrow so I hope this is correct.

[TiredofTums]

My father too served in the military and was also exposed to agent orange. Funny that you mentioned that. My mom in later years starting having Celiac Symptoms but never got diagnosed or tested for the disease. The Celiac part though I think came from my mom's side. Then passed to me and then passed to possible 4 other family members. But that agent orange is something I too question about.

I wished I could find a study on the agent orange and birth defects. Bet there are many more of us than you think!

[Gentleheart]

I too come from a huge family and extended family on both sides. I got a gluten intolerant gene from one parent and a celiac gene from the other. This year we happened to have reunions on all 4 sides of my family. That rarely happens. I honestly searched and talked all over the place trying to find even a single other relative with gluten issues or likely gluten issues. Nothing. Nobody ever heard of it, nobody had ever been tested and nobody wanted to either! Just me. I was really hoping to find at least one other person I could talk and relate to. Nope. Everyone else was chowing down at the buffet lines and I sat in the corner with my little cooler trying to act natural at all 4 reunions. I suspect there's a WHOLE lot we still don't know about the genetics of this disease.

[fedora]

I want to restate what Nesee said.

You can get half of the gene from one parent and half from the other to form the complete DQ2 gene.

The complete gene on it's own is DQ2.5

But the two seperate halves are the alpha part found on some DQ7s and the beta part found on DQ2.2(the other DQ2 gene).

If that is the case with you, then your mom could be having a reaction to gluten without being celiac. The two half genes alone can cause a intolerance to gluten without causing celiac damage to the intestines. Occasionally the half gene alone can cause celiac, but usually doesn't.

About fiber, it didn't help me either, it had gluten in it. Your moms reaction to wheat is indicitive of a problem. It gives me rashes and itching.

My father was also exposed to agent orange before I was born. When I asked him about it he said he had GI problems before that though.

HOWEVER, my father had his colon rupture 20 years later. He has not been celiac tested(can get my family to test for some reason). His mom has symptoms too.

so I would bet a mixture of of genetics and exposure in his case. My sister has always been healthier than me, I was always the sickly one.

good luck

[georgie]

I found this good link

Open Original Shared Link

The two half genes alone can cause a intolerance to gluten without causing celiac damage to the intestines. Occasionally the half gene alone can cause celiac, but usually doesn't.

I only have one half gene for DQ2 but am fairly sure I had a lot of villi damage. I am lactose intolerant...I also had what appeared to be DH. So my eventual dx has been Celiac.