DF508 and S489x? Anyone with this?

[AceZar8910]

My daughter just found out she has both of these mutations anyone else with the same?

 

[GenH]

Hello,

Someone who you may know has posted in a facebook group asking about these two mutations, and I answered with this information:

S489X is a nonsense mutation that has a stop codon at position 489 of the protein, so at this point the protein stops being made. This means there is pretty much no functional protein at the cell surface. http://www.cftr2.org/mutation.php?view=general&mutation_id=109

As a F508del heterozygote (means one copy of F508del) the medications being developed by vertex may help (VX661 & Kalydeco + future medications, also maybe VX809 & Kalydeco if they can improve the dosage). Medications that help with read through past the stop codon might help the S489X (Ataluren has had mediocre results, but other meds are being developed).

Gen

 

[anien2]

GenH, where did you find all that info about the position of the stop codon of a nonsense mutation?? my kids have the Q890X and I havent been able to find anything about it, can you tell where can I find information about it? it is said that Ataluren works better on UGA stop codons and I would like to know what kind of nonsense mutation have my kids.

Thanks.

By the way, who else is working on meds for nonsense mutations??

And now for extra credit: do you know anything about the Ataluren phase 3-B??

Thanks again.

 

[GenH]

GenH, where did you find all that info about the position of the stop codon of a nonsense mutation?? my kids have the Q890X and I havent been able to find anything about it, can you tell where can I find information about it? it is said that Ataluren works better on UGA stop codons and I would like to know what kind of nonsense mutation have my kids.

Thanks.

By the way, who else is working on meds for nonsense mutations??

And now for extra credit: do you know anything about the Ataluren phase 3-B??

Thanks again.

I did not read that info anywhere, I studied genetics at uni for 3 years so I learnt about naming genes. There are some basics that apply to genes, the letter at the front is the amino acid that is supposed to be there, the number is the position of the mutation and the letter at the end is the 'mutation' ie the amino acid or stop codon that is not supposed to be there.

So with Q890X the normal Q (which is the amino acid called Glutamine) at position 890 is now a stop codon.

In the second image you can see how there are three types of stop codons, with three different sequences (this sequence is made up of bases). This mutation is caused by a C being changed to a T at the dna base position 2668. Just to make things more confusing the T in the DNA is represented by a U in the table. I then looked up what is normally in position 2669 and 2670 to figure out what comes after the U (hence what type of stop codon), the next two are AA. So that makes it UAA. I'm not sure about the two other questions sorry. Looks like I dont get the extra credit!

http://www.cftr2.org/mutation.php?view=scientific&mutation_id=117

View attachment 116View attachment 117

 

[anien2]

Thanks for the info!! very helpfull!! you can get the extra credit anyways!!

 

[kyeev]

By the way, who else is working on meds for nonsense mutations??

And now for extra credit: do you know anything about the Ataluren phase 3-B??

Thanks again.

I think you mean the aminoglycoside studies (e.g. gentamicin), they also act on the Stop codon similar to PTC124 (Ataluren)...

 

[AceZar8910]

Thank you so much GenH