Daughter Genetic Test Results - Please read and send feedback

[Marloann827]

Hi, my name is Marlo and I need some feedback and help with my 9 year old daughter. Without putting anyone through misery reading our full story I will shorten it the best I can. My daughter has a chronic wet cough which has yet to really get diagnosed. Two bronchoscopies show major inflammation in her airways and both have provided a significant amount of thick white secretion found on the lungs. Secretions show a moderate amount of white blood cells. Infection has to yet to be determined from what. Two sweat chloride tests both showing negative for CF and now the genetic testing. Our pulmonologist says the results don't really mean anything and that his interpretations of the results are a "variant found for disease causing mutation." I have no idea what that means so I obtained a copy of the test results and this is what it notes.

Pathogenic Mutation: None detected
Variant of Unknown Significance: c-812T>g
TG Repeat/Poly T Variant: (TG)11-5/(TG)11-7T

It proceeds to say that this individual (my daughter) is heterozygous for both the c-812T>g variant of unknown significance and the (TG)11-5T variant in the CFTR gene. Then the paragraph goes into a bunch of notes that again I just don’t understand. I continue to read and I see in the last paragraph of page 1 it says “the results of this test indicate the presence of a 5T variant adjacent to 11 TG repeats. The 5T variant in combination with a known CF mutation has been associated with congenital bilateral absence of the vas deferens (CBAVD) and may also cause mild symptoms of CF.”
So I really need some help deciphering what this means. Did this say that my child may experience some symptoms of CF. I know that this is a horrible question to ask but please understand we have been battling this constant cough along with sinus infections and stomach issues for so many years with no diagnosis. UCLA Medical does not diagnosis a child that has not provided them a positive sweat test. My daughter currently on Advair, Albuteral, Miralax, Nasonex Singular and Clariton along with a daily dose of a sinus rinse. We currently do have the vest which she loves but we will be returning it as it was not covered under insurance without the proper diagnosis. No answers to why my baby girl is always coughing is the worst. Not being able to treat her is just as awful. The inhalers she takes all day does nothing for her. She is very active and a healthy looking kid. Doctors look at her and say "awe look at her, she is fine." Any feedback would be wonderful! Good health to everyone.

 

[Aboveallislove]

I can't give you too much information, but from what I understand, there are some mutations which are "possibly" CF causing and the 5T variant is one, WHEN IT is with a known CF mutation. The problem is your daughter's other mutation is of unknown significance. To me, this means it could be CF causing, it just isn't known to be, so the doctor's won't diagnose her as CF based on the 5T variant that needs another CF "known" mutations. But what happens if they later determine her other mutation is "known" to be disease causing? Nothing has changed but the doctors saying "now we know" and then they diagnosis. The important thing is the treatment, but it sounds like she can't get the vest as is. Is there any way the doctors can do a CF related metabolic disease or some other diagnosis that can get her the vest??? I'm so sorry. I wish I had more information. I'm wondering if it would help to talk with an expert at Ambry? There is a contact person here if you search--maybe even a forum just on Ambry.

 

[Beccamom]

We are in a similar situation with our 14 year old. I have a CF diagnosis with a disease causing mutation, a stop codon, and 5T variant. I have mild CF symptoms but they are getting worse with age.

We did get a vest for my daughter. The way we did this was we did 3 months of Manuel chest PT while I took FMLA leave from work. Then my mom watched my daughter who was on homebound instruction (FEV1 was 50%). My mom has MS and physically could not due chest PT. Her FEV1 increased to the 70s in the three months of Manuel chest PT. The pulmonogist told me it was in my daughter's head that the PT worked. We stopped for one week then took her to the pediatrician where he witnessed her cough returned. With the pediatricians note that Manuel chest PT worked, a letter from my job that I had taken my max unpaid time off work, and a note from my mom's PT that she physically could not do Manuel chest PT we got the vest approved. I wish you the best. It has been 3 years since my daughter's FEV1 hit 50%. And this June she bad a 103%. She is consistently only dropping to the 90s when sick and bounces back with antibiotics based on sputum culture and increased vest and hypertonic saline Neb. Best wishes.

 

[Beccamom]

I forgot to mention my daughter has my known disease causing mutation and 7t 9t variants. Her official diagnosis is COPD Chronic Bronchitis type. My other daughter is healthy with my 5t variant and no mutations.

 

[Marloann827]

Thank you so much for taking a moment to respond. Your explanation was wonderful and now I get it. You made it make sense for me. Thank you.

 

[Julie7]

There is a really good explanation on the thread called "welcome Ambry genetics." Go to the last page and read LittleLab's comment and the last one by Ambry...so read the last 2 posts. My son has the poly 5t 12TG / 7t 11TG and 2 copies if M470v. No diagnosis but he is followed by a CF clinic. I woukd get another opinion. Maybe worth a trip to John's Hopkins or another excellent clinic. There are manybpeople on thus site with CF without a positive sweat test.

 

[Justinsmama]

We passed the sweat test and only had one disease causing and double 7t (something or other) and three polys of unknown significance until this Feb when one of the "unknown" was reclassified as disease causing. He had been diagnosed at Hopkins off of the 1 mutation and clinical. Now we are genetically confirmed. It may be that they will find out information about your unknown. Prayers to you and I would see Hopkins if you can. Good luck!!!

 

[Marloann827]

I am in the process of obtaining an appointment at Childrens Hospital Los Angeles CF Clinic so someone can review my daughters test results with me. Her Ped Pulmonologist at UCLA has swept it under the rug and I need a better understanding of the results and what they mean for my daughter today, tomorrow and for her future. My daughters test results note that she has no detected pathogenic mutation but as noted above she has an variant of unknown significance and a TG Repeat/Poly T Variant. Is it possible that someone with CF has no detected pathogenic mutation at the time of testing? My concern is that Children's won't even see us since it clearly calls out no detected pathogenic mutation.

 

[jshet]

My son had 1 positive and 8 very high borderline sweat tests (ranging from 54-59). They have not found any mutations only polymorphisms in his genetic testing. He has all the symptoms of cf. He is pancreatic insufficient, needs enzymes, and has a g tube for night feeds. He has lung issues requiring using the vest 2 times a day and nebulized meds of pulmocort, albuterol, hypersal twice a day and pulmozyme once a day. He has developed osteoporosis which is also seen in cf and is now receiving infusion therapy to try and slow this. Therapy may last 3 years.
My son has a diagnosis of cystic fibrosis. His cf doc. is at the top of his field with and had written the book cystic fibrosis a guide for patient and family.
This is what he has said to me. Cystic Fibrosis can be diagnosed clinically. Your son has a positive and many high borderline sweat tests. He has all of the symptoms and more importantly is responding to all of the treatments. It can be diagnoised without knowing his mutations, because they may not have been found yet, and while his polymorphisms are not considered disease causing now, this may change in the future.
My son is 17 and his diagnosis is cystic fibrosis with pancreatic insuficency. Hope this helps.

 

[Marloann827]

This thread is the beginning of many eye openers for me. Thanks everyone for contributing wonderful information. I wish you all the best health you can have each and every day.

 

[njlins]

I can tell you this. I participated in a study to determine my second CF gene as it was only identified as a 5T varient before. The MAP study (mutation analyis project) came back with the this 5T varient having a 5T TG 12. If the 5 T had a 12 or 13 varient then it was significant when paired with another known CF gene. I also have the Delta F 508 gene and I also had a high sweat of 82 and 84 on the two different arms. So via the genetics and sweat test I am a confirmed case. Truly so sorry your daughter is suffering so much and I know this is extremely difficult to be helpless to find a cause. It must be hard when the sweat test and genetic tests are not positive. Oh, I also have the 9T varient but was told that this was insignificant. Why they tested for this then is strange. I am almost 70 but did not have lug issues until age 53. I did suffer with extremely severe sinusitis all my life.