View Full Version : Curious about thoughts on these mutations

04-18-2017, 08:09 AM
Hello! I'm kind of new here, been reading posts for a while but was not able to post until recently.

I have a nineteen year old daughter with the following mutations:

Ambry Full Gene Analysis: Variant, likely pathogenic: p.L375F; variants of unknown significance: none detected; TG Repeat/Poly T Variant: (TG)12-5T/(TG)10-7T. No gross deletions or duplications found.

Further testing revealed that one gene mutation is from me, and one from my husband.

Her symptoms are primarily gastrointestinal (had her gallbladder removed when she was fifteen and continues to be plagued with nauseousness and abdominal pain) although she also has coughing and choking episodes. She has been diagnosed with Postural Orthostatic Tachycardia Syndrome and salt tablets have improved her symptoms quite a bit. Her two sweat tests have come back as one at below 10/the other at 10.

We have been searching for an answer for her illness for years, and these mutations are the only thing that's come back as abnormal. We've had several doctors tell us it can't be caused by these mutations, but one doctor thought that it could and put her into the CFF registry, but has no plan of management to help her feel better.

So, I was curious what people on here thought of this data. Would appreciate any insight.

Thank you!


05-09-2017, 08:02 AM
It's been a few weeks since I posted this, and have received no replies.

I have been unable to find anything in the research on these mutations together, so am thinking that there aren't any documented cases? The poly T/TG is fairly common, but from what I've read the L375F is mainly associated with vas deferens absence or malformation. My daughter had an endoscopic ultrasound done last year, because they were not able to visualize her pancreas well. The findings on that showed hyperechoic strands and foci throughout the entire parenchyma, and her main pancreatic duct was extremely narrow at 0.5-0.6 mm. The doc that performed the procedure told us that all of that was within normal parameters. I'm thinking however that maybe the narrow duct could be causing her abdominal pain. But I've had doctors tell us that at her age those mutations should not be giving her symptoms, maybe if she were 50 or 60, so we should keep looking for answers.

I would really appreciate anything you guys have to offer, as I am not sure how to proceed. Could a rare mutation, that ambry states as most likely pathogenic, combined with the 5T/12 TG variant be the culprit? Even though her sweat chloride levels are in the normal range?

05-09-2017, 10:32 AM
I'm sorry none of us really seem to have answers for you. I'm completely clueless. The only question I can think of to maybe help is is your daughter being seen at an accredited Cystic Fibrosis Center?

05-10-2017, 12:33 AM
Thank you for responding Kenna2.

I have a biochemistry degree, and I'm generally pretty good about researching things, but I just can't find anything on this. Yes. We have been to an accredited CF clinic, National Jewish, which gave us mixed reactions to the genetics. One doc said yes it could cause it, but gave us no management plan. Another told us that it's probably not the CF and didn't wanted to delay another diagnosis. Her immunologist at Jewish, who is not part of the CF clinic, but seems to at least want to understand genetics, also told us it can't be CF. Either way, we have no way of managing it. She is constantly nauseous with abdominal pain and very little appetite.

CF is the only thing in the last five years that has come back "abnormal" at all, and we've seen just about every specialist there is. I'm the one that went down this road because of research I've done. I had to fight with the doc at Jewish to order the genetic testing because he didn't believe she would have any mutations with the normal sweat chloride
- even though at our first appt he told us that clinically she presents with it.

I realize no one on here will have experience with this mutation combo, but figured the combined experience of the community may help us.

05-10-2017, 09:12 AM
I'm so sorry she is suffering through this. The stomach pain and things could possibly be the result of a lack of enzymes. I also wonder if she might be experiencing some sort of reflux as well. I know when I was suffering really badly from GERD, my stomach and cough were a mess. The acid was getting into my lungs and making me sick. I had to have a Nissen surgery to correct it. Like I said, I would follow up with a Gastroenterologist because they might be able to get her started on something to help relieve that. At least maybe start her on enzymes.

05-10-2017, 09:38 AM
She's being seen by a gastroenterologist. We have tried going down the reflux route but it didn't help her symptoms. Her fecal elastase was in the 400 range, so she's pancreatic sufficient? He tried her on zenpep, but it made her really sick. Come to find out two years later that she's allergic to pork, and those are porcine derived. I've thought about trying a vegan alternative of some sort. But with her elastase level as high as it is, would they help at all? Can the pancreas sometimes be working ok and sometimes not? I know that her stools are generally very loose, but for whatever reason, the day we sent that sample in they were hard. So, I sometimes question the results.