Mutation classification

Question

There is hardly any information on the 2184delA mutation other than that it mainly occurs in Ukraine.

Which class does it belong to, and what is the difference to the similar-sounding 2184insA mutation?

Answer

Hello,

The 2184delA mutation, like the 2184insA and other mutations, is located in a section of the CFTR gene where the building block A (adenosine) usually occurs seven times consecutively. Due to the loss (deletion) of one A (delA) or the insertion of an additional A (insA), this section contains only six (or eight, respectively) A building blocks. In both cases, the so-called open reading frame is lost (since three consecutive building blocks of the DNA are coding for one amino acid, the genetic code becomes mixed up by the loss of one building block). Due to the loss of the reading frame, a premature stop codon is created at the end. This mutation best fits into class 1.

There are mutation class-specific drug therapy approaches for some of the class 1 mutations. However, in contrast to those stop mutations where a premature stop codon is created due to a so-called nucleotide exchange, the drug Ataluren (PTC124), which leads to a “reading” of a premature stop codon, would not be suited for the 2184delA mutation.

As a class 1 mutation, 2184delA can be considered a “typical” CF mutation, i.e. clinically, 2184delA homozygous patients or F508del/2184delA heterozygous patients can expect a similar disease spectrum as an F508del homozygous patient.

Kind regards
Prof. M. Stuhrmann-Spangenberg

15.05.2012