Explanation of genetic testing

Question

Explanation of genetic testing: heterozygous deltaF508 in exon10 and c.1657C>T (p.Arg553X)

Hello,
the genetic testing of my son showed the following result: "Heterozygous for the mutation deltaF508 in exon10 and c.1657C>T (p.Arg553X). CF has been diagnosed before via sweat test."
According to my knowledge until now "heterozygous" means that there are different mutations.
In one "gen" the deltaF508 and in the other "gen" the c.1657C>T (p.Arg553X)? Unfortunately I am not able to find anything about the second mutation.
1. Did I understand it right?
2. Could you give me some more precise information about the second mutation (to which class does it belong)?
3. Could you tell me how the effect of both mutations together would be?

Many thanks!

Answer

Dear questioner,
yes, you did understand the result of the genetic testing right - heterzygous means that the test shows 2 different mutations in the illness-causing gen CFTR. F508del "the 508th aminoacid, acutally a Phenylalanin (=F) is missing; the abbreviation „c.1657C>T (p.Arg553X)“ is a bit untypical and lingustically slangly confused. It means "at the position 1657 of the protein (=c.) coding sequence a cytosine (=C) has been replaced by a thymidine (=T) and therefore there is now at the 553th aminoacid position no Arginine (=Arg, or in the one letter code for aminoacids R) but a stop codon (=X)". This mutation is well known under the abbreviation R553X (class I mutation).
F508del and R553X are both typical CF-mutations, i.e. the clinical picture is expected as classical CF. It can be expected verbally from the stop mutation R553X, that the CFTR-protein stops not on schedule at the aminoacid 553, will be too short and does not function. Indeed the cell is realizing this and destroys the messenger-RNA, so that no transcript is produced at all from the mutation R553X.
Many greetings,
Frauke Stanke

23.04.2013

23.04.13
In general, mutation analysis only gives a rough direction but it has to be clearly stated that the individual clinical course and especially the degree of lung involvement cannot be predicted according to the genotype, as many other genetic (modifier genes, etc.) and environmental factors play a role and the severity of disease differs substantially even between patients with the exact same mutations. Therefore, it is very important that the individual patient is seen regularly in a certified CF center and follows his individual treatment program.
D. d'Alquen