Meaning?? Heterozygous form in carrier test

[mdertinger]

3 years ago my husband's brother had a baby diagnosed with CF. I was pregnant at the time, so my husband and I went for CF carrier screening. My test stated negative for the cystic fibrosis mutation. My husband's test stated that the "delta F508 CF mutation in heterozygous form" was identified, meaning he was a carrier.

Recently he has lost a lot of weight. He is taking Adderall for adult ADD, which is a stimulant, so we thought the weight loss was normal. But he is continuing to lose weight, so he went for a physical. They found a high level of an enzyme called Lipase, which is a pancreas enzyme. I've done some internet research, and I'm beginning to suspect he may be experiencing "carrier symptoms". However, I'm also wondering if he might actually have the CF disease!

He is 29 years old. He has never had any lung/sinus problems, but he has had Irritable Bowel Problems in the past. Ironically, he says his IBS has been better since taking the ADD meds. He thinks it's cuz he can focus better and is less stressed. He went for a CT scan today. I think they are looking for blockage in the pancreas or problems with the liver.

My question is, what does the "heterozygous form" mean in his carrier test? Also, would a sweat test be sufficient to diagnose a mild case of CF, or should he just go ahead and get the blood test?

Thanks, Maria

 

[anonymous]

Maria,

genetics are hard, heterozygous by definition is 2 different forms of a particular gene. In you husbands case 1 is normal, 1 has a delta F508 mutation

Its hard to illustrate here but: If you have two carriers X= normal CF = cystic fibrosis

X CF

X CF

25% chance homozygous normal, (X+X=XX) line down though the X's
25% chance homozygous CF, (CF+CF =CFCF) line down through CF's
50% chance heterozygous, (CF+X)2, diagonal through X and CF


You and your husband

X CF

X X

50% chance homozygous normal (X+X)2 line through X's
50% chance heterozygous (X+CF)2 line from X's to CF

confusing I know....But if your husband is heterozygous he has only one know defect. There are many mutations though, more and more each day, I would suggest another genetic test through a reputible lab to be sure he doesn't have a more rare mutation on the other side.

Do you know what type of defect the baby has?

luke

 

[anonymous]

Thanks for the explaination. So if he has another, rare mutation on the other side, then he might have CF?

It would be so strange, since he hasn't really had any symptoms except for the weight loss, and now this elevated pancreas enzyme. I'm assuming that if he's had no real symptoms, if he does have it, he has a mild case, which would mean a continuation of mild symptoms and no real early death prognosis.... am I kidding myself??

When he got back from the CT scan, I told him what I read about carriers having symptoms, and persons with CF not being diagnosed until adult. He wondered if he should get more life insurance before he takes a sweat test.

I don't know what mutation the baby has. My husband's brother and his wife are kind of closed about it. They have 4 kids. The 2nd has CF but they've never tested the other kids.

Maria

 

[anonymous]

Maria,

My mom has Delta F508 in heterozygous form. She has a very difficult time digesting fatty foods like pizza or popcorn. I've always heard of carrier symptoms and my mom definitely has them.

Dad and his side of the family have a lot of allergies and sinus problems. Dad has Delta F507A. CF related? Who knows. Could be.

Just cuz a gene is recessive doesn't mean that it doesn't exhibit some expression. Being a CF gene carrier is probably a good example of this.

 

[anonymous]

Maria,

If your husband would have a rare defect, then yes he would have CF. If it makes you feel any better I do not think that it is likely. As for life insurance, you can never have too much no matter the scenario. I can tell you that you will not be able to get it nearly as cheap or at all on a private policy should he be diagnosed..


Luke

 

[anonymous]

So does it matter at all what type of mutation a person has with regards to severity of symptoms or the type of symptoms (i.e. lung vs. digestive)?

I read in one post that the delta F508 mutation is more apt to cause digestive symptoms. Is this true?

If my husband knows he carries one mutation (delta F508), how important is it that he be re-tested to see if he carriers another, more rare mutation? If he does carries some other, rare mutation, does it matter which one? I guess what I'm asking is, do specific combinations of mutations typically cause specific symptoms? Or is it really just a toss up?

Thanks, Maria

 

[anonymous]

Maria,

Yes, it would matter if he got retested. If he got tested and was found to be positive he would need to be treated as such. Treatment is the key to our longevity. If you are unsure of what to do please follow up with your doc. My advise, always better to be safe than sorry. Retest and take it from there


luke

 

[anonymous]

I've only been at this site for a couple of hours, but yes, Luke, you did make me feel better. You seem to know quite a bit about CF.
I know I'm probably worried for no reason, but then I read all those other posts from people that found out they had CF at the age of 28, 32, 44!!
Thanks, Maria

 

[MasonsMom]

My husband and my son both are considered "symptomatic carriers". They have DeltaF508 AND another rare mutation both, but these 2 mutations are on one chromosome. I have been told that this is highly unlikely to happen, but we have the proof from Ambry. My husband has had sinus problems and digestive problems his entire life. He was also diagnosed with IBS, but we now know his digestive problems are CF related. I would suggest having an expanded test done for your husband. Even if it does come back that he is a carrier, he can still benefit from enzymes etc. I know these have helped my son alot. I wish you all the best!

Velvet

 

[anonymous]

Velvet,

that is a genetic wonder, huh...never heard of that one. I wish your men well


luke

 

[MasonsMom]

Thank you Luke! I am hoping someone else may have heard of this and be able to give me more information though. I went and got the paperwork from Ambry, and the 2 mutations found are deltaF508 and I1027T. The language used from Ambry is "that these mutations are located on the same chromosome in this family. This patient is a carrier of the mutations listed above". I know our doctor had never seen this happen before, so perhaps someone on here has some knowledge about it. Thanks!

Velvet

 

[anonymous]

Now I'm back to worrying! My husband's father is dead and his mother is a hypocondriac and a chronic lier who claims she has Lupis, so it's hard to figure this stuff out. Does anyone know of a CF-Lupis link?? My father-in-law died a couple years ago from heart failure after spending weeks in the hospital for "unbalanced blood chemistry". He had a very high level of white and a very low level of red blood cells, but doctors could find no reason for it. They gave him steroids to increase the red cells and sent him home. His heart just stopped the next day. Granted, he drank hard liquor every day his whole adult life. He also suffered from asthma (as does my husband's brother).

I guess what I'm getting at is that both of my husband's parents could be carriers, or may even had/have mild cases of CF, increasing the chances that my husband has CF.

So Velvet.... why did your husband and son get tested for CF in the first place. Do you have another child or a sibling with CF?

So this concept of "symptomatic carriers", am I going to have a hard time convincing our GP that my husbands should have an indepth genetic mutation analysis done?

Also, if your husband and son carry the DeltaF508 AND another rare mutation, doesn't this mean they have CF, rather than they are carriers? Is it because these 2 mutations are on one chromosome, and to have CF you need these two mutations to be on two different chromosomes?

Also, this Ambry lab, did I read that this lab tests for many more mutations that other labs. Do you have an address?

Thanks for any info you can send my way!
Maria

 

[MasonsMom]

Maria - My son was tested because he had a meconium plug at birth, and at his 2 week check-up he had a significant weigh loss termed failure to thrive. These two symptoms combined gave his pediatrician worry so she had a dna test done. This was a general test that looked for only the most common mutations. When that came back positive for 1 deltaF508 mutation we were sent to a pulmonologist that ordered a sweat test which came back at borderline with a 44.68 and a 40.95. The pulmonologist then ordered an expanded dna test from Ambry genetics which found the second mutation I1027T. However, at that time Ambry could not determine if these mutations were on different chromosomes or not. So my husband and I had our blood drawn and sent to Ambry for family studies. That is when they determind that both mutations came from my husband. From what I understand, having 2 mutations does mean CF, unless those mutations are both on one chromosome. If they are both on one side, then that means that one side functions "normally" and therefore you are a carrier. I guess it is somewhat of a genetic anomally. However, both my son and my husband do have symptoms, hence the term "symptomatic carriers". The doctors are keeping a close eye on my son because this is all new and they aren't sure exactly how he will be affected throughout his life. And apparantly there is a possibilty that the mutations at some point could decide to split. I get very confused at times trying to learn all that is going on, and luckily our doctor is very patient and very knowledgable and is helping us greatly to try and understand. We just have to take it one day at a time, like everything else in life.

As far as getting you GP to do an expanded test, I'm not sure how you would go about getting that done. You might try contacting an actual CF doctor and meeting with him to explain the family history etc. Ambry genetics is now capable of testing for 1200 CF mutations according to our pulmonologist. And as far as I know, they are the only ones currently doing so. A sweat test may be something else you could have ordered by a CF doctor that a GP wouldn't.

I hope this helped somewhat, and although I am new to all of this and don't have very many answers, I am definitely willing to help you out in any way that I can.

Velvet

 

[anonymous]

Wow, how weird! So you tested negative for any CF mutations and your son picked up both from your husband. Has Ambry or your son's doctors ever heard of this before, or are they the only one they know of??

I was just on the phone with my sister in law telling her about your case. Her second child was diagnosed via blood/DNA at birth because she had a meconium plug. The results showed she had two delta F508 mutations. She assumes that both her and her husband carried those mutations, but they've never been DNA tested. She had her amniotic fluid tested when she had her 3rd and 4th children, but they only tested for the DF508 mutations. The 4th child is a carrier of the DF508 mutation, but they only found the one mutation they tested for. However, the 4th child has shown symptoms since she was born, so at 2 weeks they did a sweat test, which was negative. But she says the ten month old baby still has very loose stools, chest congestion, and some wheezing. She wants to have a second sweat test done. And even though she has been seeing a CF doctor and attending CF support groups for her 2nd child, she had never heard that carriers could display symptoms.

After I told her about your case, we are thinking that possibly she or her husband have two mutations, maybe on the same chromosome, like your husband. And that maybe the baby inherited the DF508 and a second mutation, not detected since no other mutation was tested for. For my family, this could mean my husband could also be a "symptomatic carrier". I know all this would be extremely rare, but who knows. I will definetely suggest that my sister in law get the baby tested again.

Thanks much for the info... you've been very helpful. It really amazes me that internet has brought so much information to patients and families that was never available before.

Maria

 

[MasonsMom]

Yes, my son got both mutations from his father and I carry no mutations. Ambry genetics from what I gather is aware of the happening because on my paperwork from then regarding my son's testing it says "The deltaF508 and I1027T mutations have been known to occur on the same chromosome in many families." I would interpret this to mean that it has been seen before. For this reason, we had the family studies done.

From what I've gathered from other posts on here, the idea of symptomatic carriers isn't actually a new idea, just perhaps newly "accepted" in the medical communities. My advice is to be persistent. You can't fight your enemy until your enemy is identified, so to speak.

Velvet