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The 5T Mutation in the CFTR Gene

Dear Editor

I have just been diagnosed for being positive for the 5T allele in intron 8. I am negative for the main gene of CF, but the 5T allele is a mutation of some sort in CF. How can this affect my children? What if my husband has the same gene? What if he doesn't?

Natasha Trajkova
New Jersey, USA

Professor Dieter Gruenert, a Genetics advisor to IACFA replies:

There is limited information correlating genetic anomalies in the CFTR gene with specific phenotypic/pathological characteristics. What is known about the 5T mutation, is that it causes abnormal splicing of the messenger RNA (mRNA) (i.e., the way that the pieces of the gene that give rise to the mRNA are put together) and that there
appears to be lower levels of the CFTR mRNA expressed from the chromosome carrying this particular mutation. If it occurs without any other pathological mutations in the CFTR, in most cases there does not appear to be any associated 5T-specific pathology.

There have been reports of exceptions with regard to the question of pathology that appear to be dependent on the overall genetic background (i.e., not all genes are expressed in the same way in all individuals thus giving rise to variations in the genetic
background). There are scattered conflicting reports as to the contribution of the 5T mutation to the lung function anomalies.

Overall, the consensus is that the 5T mutation alone is not pathogenic, but if it is associated with CFTR pathogenic mutation, there may be an associated pathology that could be manifested in male infertility or mild lung function anomalies.

I hope that this helps answer some of your concerns.

GLOSSARY
Anomalies = Differences
mRNA = messengerRNA = The genetic information taken from a gene responsible for the protein.
Pathological = Disease
Phenotypic = How genes are expressed in the individual
(e.g. you may have the genes for blue eyes, but still have brown eyes or phenotype)