What is the Poly T tract?

The Poly T tract is a string of thymidine bases located in intron 8. It can affect the efficiency with which exon 9 is spliced. There are three common variants of the poly T tract: 5T, 7T, and 9T. Both 7T and 9T are considered polymorphic variants and 5T is considered a variably penetrant CF mutation.

 

What does the 5T variant do to CFTR?

The 5T variant is thought to decrease the efficiency of intron 8 splicing.

What is the TG Tract?

The TG tract lies just 5' of the T tract. It consists of a short string of TG repeats that commonly number 11, 12 or 13. A longer TG tract (12 or 13) in conjunction with a shorter T tract (5) is thought to have the strongest adverse effect on proper intron 8 splicing.

 

Which patients are appropriate for T/TG tract typing?

Males with CBAVD or suspected CBAVD. patients with non-classic CF or carriers of 5T who wish to further refine their reproductive risks are all appropriate for T/TG tract typing. 5T and TG tract typing should not be included in a routine carrier screen.

Can you assess a specific risk in each patient?

This analysis is not able to provide a specific risk figure for developing symptoms or having a child that develops symptoms of non-classic CF or CBAVD. It is able to assign a magnitude of risk as increased or decreased. A person with delta F508 and 5T/11TG is less likely to develop non-classic CF, but it is still possible. Conversely, a patient with deltaF508 and 5T/13TG is more likely to develop non-classic CF or CBAVD, though this is not a guarantee.

 

Where can I read about the original study of TG tract length and a non-classic CF phenotype?

Groman et al (Am J Hum Genet, January 2004) studied the TG tract length in symptomatic and asymptomatic individuals. A longer TG tract length was much more likely in symptomatic individuals. It is worth noting that the risks assessed by T/TG tract typing apply mainly to males and the development of CBAVD. A limited number of females was included in the original study.