husband is a carrier

[anonymous]

Hello-
my husband has absence of the vas deferens with both genes mutated. He tested negative on the sweat test however. because he has no vas deferens we underwent invito fertilization with ICSI. I was tested for the genes and told I have niether, so they allowed us to undogo the procedure with the unliklyhood that our child could have CF.
Since our daughter was born she has had many lung infections and was sent to a pediatric hospital. While there she was diagnosed with juvenile asthma, but at 18 months showed asthma signs of a 6-7 year old. Because of this and several other signs pointing to CF she will be having a sweat test this coming week.
For abvious reasons I am terrified. I was wondering if anyone out there has had the same problem.
Does anyone know the odds of her having CF and the odds of her being a carrier like her father.
We also cannot figure out how her father has the double gene mutation but not CF.
I know I sound very confused, I was just hoping that someone who has been there might read this post.

Thank You

kathy Rossiter

 

[NoDayButToday]

Having two mutated genes means you have CF. Regardless of what your husbands sweat test results were, some people with CF have certain mutations that do not cause a positive sweat test result. His absence of vas deferens only makes it more likely he does have CF.
If you tested negative for the genes, it is HIGHLY unlikely your daughter has CF (since if a non carrier has kids with a carrier/patient, the child will definitely NOT have CF). But there are many mutations (over 1000), and unless your genetic testing tested for all of them, there is a small possibility you are a carrier. So it is worth it to get her sweat tested if she shows symptoms, as well as an Ambry genetics test for both you and her.

 

[anonymous]

I agree with Coll, if your dh has two cf mutations, then he has cf no matter what his sweat chloride result was. He just may have a milder version of it at this point. Also, on the genetic testing, definitely find out what lab and how many mutations they tested for. If it was anything other than Ambry, you could still be a carrier and it is possible your dd could have cf. It's a good thing that she's being tested. If I were you, I'd request that your dh and your dd be seen by a cf clinic to determine whether they have it or not. Good luck and please keep us posted. Also, remember that while there are a LOT of children tested for cf, few actually have it so the odds are in your favor. If, however, she does have it, you'll see great improvement in her health when she's treated properly. Good luck!

Oh, one more thing, do you know which mutations your dh tested positive for?? If so, if you post them, we may be able to help you determine whether they are both cf mutations. Last thing, was your dh sweat tested at an accredited hospital? If not, a false negative is possible. Also, do you know what his #s are? If he fell on the high end of normal (30+) or in the borderline (40-60), it's possible that the drs read it as negative when it may not actually be. I hope that helps.

 

[anonymous]

If your husband has a double gene mutation he has CF. There have been many cases of negative sweat chloride tests - the only true way to know if someone has CF is through genetic testing which is sounds like your husband had done. If your genetic testing was negative there is no way that your child could have CF. However, you state that "I was tested for the genes and told I have neither". Were they only looking for the same genes that your husband had? If they did not do the expanded assay and look for all CF mutations and only looked for a match to your husbands - then you could be a carrier.

 

[anonymous]

Kathy, as everyone else has said you husband DOES have CF. Regardless of the chloride sweat test level, if he carries two mutations, (whether they be the same mutations or different mutations) he as CF. Carriers only have ONE mutation.

That being said and out of the way, when you had your carrier test, how many mutations did they test for. I am in the same situation as you, My husband has two CF mutations and therefore CF and we are going through IVF with ICSI in October. At first, I had a local carrier testing where they tested 28 mutations. They I had a more elaborate one (although not by much) which analyzed 86 mutations. I am still not satisified with that limited testing considering there are over 1000 CF mutations, so now we are waiting for insurance authorization to covery the AMBRY genetic test (www.ambry.com).

To answer your question, it's been established your husband has CF because he carries two mutations (he may have a VERY mild case which is very likely, or may have just reproductive involvement and not lungs or pancreas, this is also common). If the testing you had was limited there is a chance that you are a carrier. If that is the case, your husband has CF and you are a carrier, your children have a 50% chance of being affected (having CF) and a 50% chance of being an unaffected carrier (Just carries 1 mutation).
Now lets say that for some reason your husband's genetic testing was wrong and he is just a carrier, having only 1 mutation and your genetic testing was wrong too and you ARE a carrier, so both of you are carriers, your child has a 25% chance of being unaffected, 50% chance unaffected carrier, and 25% chance of having CF.
And then the third scenario would be that he has CF (2 mutations) and you are NOT a carrier (Zero mutations), your child has a 100% chance of being an unaffected carrier.

It would be my recommendation that your daughter have not only a sweat test, but also very thurough genetic testing. Ambry Genetics is the ONLY labratory which tests the CF Gene it it's entirety. It is likely that your daughter does have CF.

Also, after re-reading the information you posted, I noticed you put "I was tested for the genes and told I have neither". I have a few questions about this, #1, did you get tested by an accredited CF center or just by whatever infertility doctor you were seeing? #2, are you aware that you don't have to carry the same mutations your husband has to pass the CF gene onto your children? Meaning that your child can get one of the two mutations your husband has, and if you are a carrier, you can pass whatever mutation you carry, even if they are not the same. If you have more questions and want to email me directly, please do so at division902@hotmail.com.


Julie (wife to Mark 24 w/CF)

 

[anonymous]

Thank you very much for your response to my post. I was wondering if either of you know where We can go to locate a CF facility. I suppose the pediatric hopital can refer us though.
I think we are going to have my husband retested and this time I know enough to ask for this ambry test.
Also, my daughter will be put in a hot room and made to sweat, not the chemical with electrodes I have read about, have either of you heard of this?

thank you again for your help. I feel much better since finding this website.

Kathy

 

[luke]

Kathy,

We had a discussion about a smiliar topic a while back that you might find interesting reading, particullary MASONSMOM's post. If you have specific questions let me know and I will attempt to answer them.

http://forums.cysticfibrosis.com/messageview.cfm?catid=5&threadid=2255&FTVAR_MSGDBTABLE=



Luke

 

[thefrogprincess]

Go to the CF Foundation's web site www.cff.org to find a CF center near you.

 

[MasonsMom]

Kathy,
Both my son and my husband have double mutations, yet do not have CF. Mason (my son) had a sweat test done at just a few weeks old and it came back as borderline. We followed up with more testing, and finally had the Ambry test done. This is where both mutations we identified as deltaF508 and I1027T. The Ambry paperwork from his test acknowledged that they could not tell whether the mutations were on one chromosome or not. In order to determine this, my husband and I both had to have our bloodwork sent to Ambry. It was then that they identified both mutations also in my husband. It was therefore determined by Ambry genetics that both my son and my husband are CF carriers with 2 mutations. They both have symptoms, mostly digestive. My son has not as of yet manifested any lung problems, but my husband does have asthma. So yes, although I guess it is highly unlikely, it is possible to have a double mutation and still be considered a carrier. We use enzymes on Mason, and he also requires a high calorie diet. Definitely follow through with having Ambry testing, and if family testing is in order, go through with that as well. That is how we finally got our answers. I wish you all the best, and please feel free to contact me by email at velvethardy@sbcglobal.net if you would like any more information from me.

Velvet

 

[anonymous]

Luke,

After speaking with the doctor who has my husbands results I found and I quote"he is a carrier with deltaF508 and R117H mutations"
Because he is a carrier and I have no mutations in a general scan they claimed that we should have genetic counseling, but our chances of having children with CF are no larger than eneyone else.
After reading all I have on this sight in the last two days this seems a little impossible.
I have contacted a counselor, but have not received a call back. I was wondering if you could shed a little light on this two mutations thing.

Thanks,'
Kathy

 

[NoDayButToday]

To find a CFF accredited center to have the sweat test done at, visit CFF.org. I think it is slightly unusual to literally overheat the child in a stifling room to do the sweat test; I think the probes/electrodes method probably produces a better sweat sample given that it is coming from one area.

 

[anonymous]

Kathy,
Here's a link to a database of all of the cf genes: <a target=new class=ftalternatingbarlinklarge href="http://www.genet.sickkids.on.ca/cftr/">http://www.genet.sickkids.on.ca/cftr/</a>
Also, as you're probably already aware, DF508 is the most common gene. Here's the info in the database for R117H:

-Two patients (5y and 13y, males), the second one diagnosed at 1y, the first one with mild pulmonary disease, swat chloride 58-92mmol/l (first one), 42-43mmol/l (second one). Both carrying delF508 on the other allele.(pers.corr. Feldmann)
-One patient (male) with CBAVD, carrying 712-1G>T (Casals et all 1995)
-39 patients, 14=the 5T group, the rest=the 7T group. 11 out of 14 in the IVS8-5T group had sweat chloride higher then 60 mmol/l and 2 of them died (ages 19 and 42years)Most of the individuals in the IVS8-7T group didn't have clinical CF. Lung disease varried from none to moderate. Most of the patients were PS. 34 individuals carried delF508 on the other allele, one was homozygous for R117H, 4 had unknown other mutation. See article for details(Massie et all 2001)
-3 patients (females, ages 5,4 and 2), sweat chloride 34-55 mmol/l. 2 of them with recurrent upper airwaiys infections(delF508 on the other allele), no pulmonary symptoms in the one with L997F on the other allele. (Padoan et all 2002)
-The results strongly suggest less sever CF phenotype associated with this mutation(Ferec et all 1993)
-Male infertility as the only presentation associated with homozygous R117H (Bienvenu et all 1993)
-21 patients were compound heterozygous for R117 and delF508, which was the most frequent CAVD genotype(Dork et all 1997)
-One individual, female, infant, heterozygous for R117H and delF508, asymptomatic - tests done such as sweat chloride, bronchoscopy with bronchoalveolar lavage, nasal transepithelial potential diference were consistent with findings expected for a normal individual. (Chmiel et all 1999)
-R117H was found in all affected members of 5 families with hereditary pancreatitis.(Ravnik-Glavac et all 2000)
-R117H seems to be more frequent in Ireland (Schwarz et all 1995)
-R117H associated with delF508 was found commonly found in CAVD patients (Jezequel et all 1995)
-one patient with R117H, normal seat chloride and allergic bronchopulmonary aspergilosis (Eaton et all 2002)
-late diagnosis was significantly related to carriage of R117H and pancreatic sufficiency. Weak relationship with pulmonary function. (McCloskey et all 2000)
-One PI patient. Unknown other mutation. (Walkowiak et all 2001)

As I read it, the authors are concluding that R117H <b>IS</b> a genetic mutation for cystic fibrosis that generally presents with much milder symptoms. When reading what I pasted, pay particular attention to the patients cited that have both DF508 and R117h like your dh. Most have very mild disease, many have borderline or high NEGATIVE sweat tests, almost all are pancreatic sufficient meaning they don't have GI manifestations. This is my personal opinion but your dr is misleading you. From personal experience, I can tell you that there are a LOT of drs who are absolutely clueless about cf. Please contact an adult cf clinic and get your dh an appt ASAP. Also, I just wanted to reiterate that regardless of whether your dh does/does not have cf, your child should still be tested both by Ambry genetics and sweat test; however, there's still a good chance your child does not have cf. Please keep us posted.
Mel

(CAVD - means congenital absence of the vas deferens (what your dh has), PS means pancreatic sufficient, and PI means pancreatic insufficient.)

 

[anonymous]

Okay, I am SO CONFUSED by this! I don't understand how a person with 2 mutations can be considered a carrier... I mean I understand that some people w cf don't have many of the symptoms....some aren't even diagnosed until later in life bc they are so "symptomless" but they are still considered to have CF right?????

Some people only know the names of one of their mutations because the second mutation is so rare, yet they are still considered to have CF. The R117H is not that uncommon - I know a few people who have DF508 and R117H - who have been given a CF diagnosis... Many people with R117H are pancreatic sufficient but still have CF. See why I am confused!!!

Can someone please explain this?

 

[anonymous]

Okay, I am the above poster and Mel confirmed my thoughts and cleared up my questions! Thanks Mel!!

 

[anonymous]

Here's another thing I found:
<a target=new class=ftalternatingbarlinklarge href="http://www.cysticfibrosismedicine.com/htmldocs/CFText/genetics.htm
">http://www.cysticfibrosismedicine.com/htmldocs/CFText/genetics.htm
</a>Phenotypic expression

Since sweat testing was introduced there have been individuals who are atypical. They have features of cystic fibrosis but a normal or borderline sweat test. This includes mild lung disease (Gan et al, 1995), pancreatitits (Cohn et al, 1998) and bilateral congenital absence of the vas deferens (CAVBD) (Dumur et al, 1990).

This has lead to the recognition that the spectrum of mutations in the CFTR gene gives rise to a very variable clinical phenotype that may not be predictable from the genotype.

Some mutations may act concurrently with other mutations on the same allele. An example of this is exon 9 splicing which is influenced by the polythymidine sequence of intron 8 which precedes the splicing receptor site (Massie et al, 2001). This polythymidine tract is polymorphic with sequences of 5, 7, 9 thymidines. Because CFTR missing exon 9 splicing is non functional and exon-9 splicing is inversely proportional to the length of the thymidine sequences, the 9T variant allows normal reading of the gene while the 5T variant is associated with the highest level of non-functional CFTR protein (Massie et al, 2001).The commonest polymorphism is the seven thymidine (7T) variant and the DF508 mutation occurs exclusively on the 9T variant. This variation may be important in some CFTR mutations eg R117H . The presence of R117H/508 on a background of 5T is associated with an elevated sweat test and clinical CF. R117H in association with 7T is associated with a normal, borderline or elevated sweat test and variable clinical presentation. (Massie et al, 2001; Rave-Harel et al, 1997; Kiesewetter et al, 1993).

Environment factors and the influence of modulator genes are also likely to impact on phemotypic expression..

 

[anonymous]

Sorry, forgot to sign. THat last link was also me again. To the confused poster. It IS confusing. It looks like the range of presentation with the DF508 and R117H mutations ranges from negative to high sweat tests, almost no lung issues to classic cf, pancreatic sufficient to insufficient. And, it seems to make a difference whether the individual has 5T, 7T, 9T (that part I do not understand.) At any rate, it appears to me that the original poster's dh has atypical cf but cf nonetheless. Also, I couldn't find the l1027t mutation that Velvet cited in the sickkids database which leads me to think it must be a really new mutation and must work the same way as the 5t, 7t, 9t thing (occurrs on the same chromosome as a cf-causing mutation.) Of course, since that all confuses me, that's just my speculation. At any rate, to the original poster, I wish you luck in finding a competant dr to properly diagnose your children. Oh, and just as an example of how misinformed dr's can be, my pedi who is <b>very </b> informed, keeps up to date on all the latest research in many different areas, and is in my opinion very informed, educated, etc. Anyway, when we were going through diagnosis, she said that she highly doubted my children could have cf because (1) although they are small - barely on the chart, they are not classic failure to thrive, and (2) because they haven't had frequent hospitalizations. Common MYTHS about cf. Actually, 15% are pancreatic sufficient and, as you can see from the board, the range of presentation is huge...
Mel

 

[anonymous]

Kathy,
I read that you are planning on contacting the counselor to help you understand all of this. I am assuming that you are referring to a genetic counselor. From what I understand from others in similar confusing circumstances like your own, sometimes genetic counselors do not have a lot of info about cf. They deal with many diseases and are not experts on diagnosing cf. It is best that you contact a CF center close to you and speak to a CF pulmonologist who is an expert in the field. Here is a link to find the closest center.

<a target=new class=ftalternatingbarlinklarge href="http://www.cff.org/chapters_and_care_centers/
">http://www.cff.org/chapters_and_care_centers/
</a>
Sharon, mom of Sophia, 3.5 and Jack, 1.5 both with CF

 

[luke]

Kathy,

Since you are not a carrier if you have a child he/she can only be a carrier and WILL not have CF. Even if your husband was diagnosed with CF your child would still ONLY be a carrier. As for explaining the "dual defect", I can't. When I had genetics a long time ago it was not that in depth. I am only taking Velvet's doctors word on the subject. The problem is that most "CF doctors" might not know this one, it will have to be a doc who specializes in genetics. Better yet.... Mary is getting her Masters in genetic counseling, maybe she can take our problem to class. Academians love this crap!


Luke

 

[anonymous]

It's so sad that so called "doctors" are telling people this stuff. The mutations do not have to be the same to be diagnosed as "having CF". If you have 2 mutations (different, same, single chromosome, double chromosome, etc. etc.) YOU HAVE CF. Believe me I wish this were not the case because then my child (with 2 different mutations) would not have CF.

 

[anonymous]

Luke,
I think the question at hand is whether Kathy's genetic test was a thorough test (ie Ambry, or at very least Genzyme) vs the traditional 25 mutations that are generally checked when doing genetic screening for couples. If it was the later (25 mutations only) or even Genzyme's test, then there is still a chance that she's a carrier of a less common gene and, therefore, her child could still have cf. However, if her genetic testing was through Ambry, then there is very little chance that her child could have cf. I say <i>very little</i> because <b>no</b> genetic test, not even Ambry can detect with 100% accuracy. Ambry qoutes a 96% detection rate, genzyme a 90%. I'm not sure what the rate is for the carrier test but probably at least 80% (for most caucasions anyway). At anyrate, the statistics are <b>by far</b> on her side that her child does <b>not</b> have cf since she at the very least had a negative basic screen.

To the last poster, my understanding is that there has to be a cf gene on BOTH chromosomes and that for most, that means two genes, but in extremely rare cases, or in the cases of the 5t thing, can mean two genes on one chromosome. Again though, that is only my understanding.

Kathy, good luck with the sweat testing. And, good luck getting a definitive diagnosis for your dh. Please let us know what you find out! This is a very fascinating subject to me.