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G542x/5t and pseudomonas

Good day,

Can you please provide me the symptoms that someone with the above genes can have? My 7 year old son recently was diagnosed with PA and is waiting for the results for the second sputum test. I was told that he might have more than usual sinus infections and the possibility of the absence of his vas deference. Now that he tested positive for PA should I be worried? ( I am)

Thanking you in advance

Dear Mary

Thank you for your question regarding your son’s genetics and isolate of pseudomonas.
G542X is a common CF mutation which is a Class I (nonsense mutation) and there is no CFTR protein produced / expressed at the cell surface. The 5t mutation affects splicing and leads to a lower amount of CFTR being produced. This mutation has incomplete penetrance, which means that its affect is variable. Its affect seems to be dependent on the TG tract which is another region on the CRFT gene. 5t plus 12/13TG seems to be more likely to be associated with CF symptoms, when found in combination with a CF-causing mutation eg. G542X. The 5t mutation can be found in healthy individuals, be associated with male infertility (CBAVD) or non-classical CF depending on the associated gene.
There is an ongoing learning process as we discover more about the affects of particular gene combinations. The CFTR2 website has the most comprehensive data on particular gene combinations and their outcomes.
If your son has isolated pseudomonas then it is important he have eradication therapy as per standard protocols. For any of these patients with unusual gene combinations that are expected to follow a milder course if they do develop CF symptoms they should be treated appropriately. This should be discussed with your local CF centre.
I hope you have found this information helpful.

Dr Laura Jenkins
Paediatric CF Associate Specialist

2. Variable penetrance and expressivity of the splice altering 5T sequence in the cystic fibrosis gene.
Lebo RV, Grody WW.
Department of Pathology, Akron Children's Hospital, Akron, OH 44308-1062, USA.
3. Rapid and reliable genotyping of polymorphic loci modifying correct splicing of CFTR pre-mRNA using mass spectrometry
André Schaller1,3, Thomas von Känel1,3, Benedikt Gehr2, Javier Sanz1 and Sabina Gallati1
European Journal of Human Genetics (2007) 15, 53–61. doi:10.1038/sj.ejhg.5201725; published online 4 October 2006

1. Division of Human Genetics, University of Bern, Bern, Switzerland
2.Institute of Biochemistry and Molecular Biology, University of Bern, Bern, Switzerland
The answer is edited by: Laura Jenkins