My son has not one, but two very rare mutations

[LucasMR]

My son is 11. He was not screened for CF until he was 4, and had repeated bouts with pneumonia requiring hospitalization. His primary care pediatrician thought it might be asthma, but ordered a sweat test to rule out CF. His test result from that was in the "gray area", not certain of being clear of CF, not certain of CF. We proceeded with genetic testing at the time, while hearing the CF doctors tell us that his low weight, repeated pneumonia, shortness of breath, were normal. The excuses at the time were that his weight was because one of his parents is smaller than average (his mother is 5'3"), pneumonia was "that just happens to kids" and his shortness of breath were that he was playing too hard. The CF doctors told us that there was no way that he would come back with CF mutations based on his being a hyper little almost 5 year old in the office. (He was 5, and not sick at the time he was seen by the CF doc, so of course he had more energy than when he was sick.)

He has 2 mutations, and not just that, but both are very rare. I didn't know the specifics of his mutations until recently. On CFTR2.org, one of his mutations is listed as 26 people having that mutation (L997F) and the other isn't even listed. I can't find his other mutation anywhere online, and the CF doctors he is seeing now are not familiar with it either. In fact, the CF doctor's at Children's Hospital (St. Louis, MO) have never seen anyone with this specific mutation before. The mutation is 3271+25C>T.

My son was tested this spring for pancreatic insufficiency, and will have to be retested as Quest Diagnostics lost the sample or lost the results. He does have thickened secretions, decreased lung function, failure to thrive, shortness of breath, teeth issues, recurrent pneumonia & sinus infections, and just 2 weeks ago tested positive for MRSA. (I wish this little guy could catch a break.)

Can anyone help me with where to find information on the second mutation?

Thank you for any assistance,

Luc

 

[Beccamom]

I would contact John Hopkins Hospital's genetic department. They are gathering the data for CFTR2.

 

[cramermitch]

I would contact:

AMBRY GENETICS CORPORATION (100 Technology Drive, Irvine, CA, 92618, US)
Dunlop, Charles L. M. (2233 Martin Street, Unit 422 Irvine, CA, 92612, US)
Kammescheidt, Anja (31262 Brooks Street, Laguna Beach, CA, 92651, US)

Go to: http://www.freepatentsonline.com/WO2005016251.html

They seemed to have filed for a patent on some kind of testing where his mutation is mentioned towards almost the end of the text in a few places. The filing date was in 2004. So obviously they are aware of this mutation. From the text: "Typical Failure to thrive 7T/7T variant Symptomatic 78 CFTR 17A3 3271+25 C to T 3271+25 C to T N 5T/7T variant Dx".

My son's mutations were identified by Ambry genetics and they sent me detailed information. You should ask what class his mutations fall into. This will give you a detailed explanation of what the defect in the protein is (see: http://www.nchpeg.org/nutrition/index.php?option=com_content&view=article&id=462..&limitstart=4):

I	Shortened protein	W1282X Instead of inserting the amino acid tryptophan (W), the protein sequence is prematurely stopped (indicated by an X).	7
II	Protein fails to reach cell membrane	ΔF508 A phenylalanine amino acid (F) is deleted	85
III	Channel cannot be regulated properly	G551D A “missense” mutation: instead of a glycine amino acid (G), aspartate (D) is added	<3
IV	Reduced chloride conductance	R117H Missense	<3
V	Reduced due to incorrect splicing of gene	3120+1G>A Splice-site mutation in gene intron 16	<3

1. Class I, II and III mutations generally lead to complete loss of function and a more severe disease.
2. Class IV and V cause a reduction in function and have a milder effect.