My son has been diagnosed with Cystic Fibrosis. I am not looking for medical advice regarding his condition, but I am very interested in understanding the genetic causes of his condition.

In addition to the common CF mutation Delta F508, my son's genetic testing revealed both 6T and 9T variants of the PolyT sequence.

If I understand it correctly, it seems that the variants (I have found repeated reference to 5T, 7T, and 9T variants, but almost nothing on 6T) are tied to errors in the RNA transcription of the CFTR protein, but I don't understand how, or what the difference between these variants are.

What does "variant of the PolyT sequence" mean in this context, what are the difference between 5T, 6T, 7T, and 9T, and how do they impact the production of the CFTR protein?

  • 1
    $\begingroup$ A search in both PubMed and OMIM databases did not yield any result for the 6T polymorphism. It might be not yet described. If you are really interested in the molecular details, you'll have a compendium of mostly all what is known here: omim.org/entry/602421 $\endgroup$
    – Aleadam
    Dec 22 '11 at 21:27

I haven't read too far into this, but from what I understand the variant PolyT sequence is the number of thymine bases in a short sequence within one of the introns of the CFTR gene. Introns and exons are both parts of a gene structure, but introns are spliced out of the final transcript before its converted to protein (for more information see this article on RNA splicing). Studies have shown that the presence of a 5T sequence in this region may increasethe skipping of exon 9 in the CFTR gene (there is a nice picture showing what I mean here). This exon skipping will alter the final protein product translated from the spliced RNA species.

I could not find a lot of information about the 6T allele that your son has, however, I found one short article about a patient with 6T and F508 in the European Journal of Genetics. It references another paper that talks about the length of an additional repeat sequence of GT bases and its affect on individuals the the 5T variant.

  • 2
    $\begingroup$ I can't begin to tell you how helpful this has been to me, both in understanding what the genetic diagnosis means, and what the likely impact for my son will be. I also found this paper with help from search terms I picked up from the paper you linked. While I'm not taking this as actual medical advice, it does seem like our son is more likely to suffer from CBAVD than symptomatic CF, which is supported by his complete lack of symptoms so far. I can't express how this will help in terms of hope and optimism. Thank you! $\endgroup$
    – Beofett
    Dec 23 '11 at 20:59

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