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Mutation class R352Q/2184insA

our daughter has the following mutation: R352Q/2184insA, after intensive search I could not find the class of the mutations, even not in the database
Can you tell me;
- how many people have this mutation?
- to which class this mutations belong?
- what does this mean for the course of the disease?
Many thanks,
D. R.
Dear D. R.,
about R352Q nothing can be said, this variant is very rare. It could be, that your family is until now the only one, in which this variant has been detected in the frame of a mutation analysis of the CFTR gene. If you translate "R352Q" it means, that at the location 352 of the CFTR protein that is composed of 1480 aminoacids there is no "R" (this stands for the aminoacid arginin) but a "Q" (that stands for the aminoacid glutamin). In other words, the consequence of the change change of the aminoacid at the position 352 of the CFTR protein cannot be predicted - this is only possible, if enough carriers of this mutation can be identified or if the consequence of this variant can be clarified by functional tests. One of those test is the measurement of the nasal potential difference (NPD), another is the measurement of the intestinal current flow (ICM) of a biopsy of the rectal mucosa. These measurements can be done in Germany at specialized centers in Hannover or Heidelberg.
If one would measure the resting function of the CFTR variant R352Q by these tests, your question about the mutation class could probably be answered partly.

2184insA is more easy to explain: 2184 is a typcial CF-causing mutation of class I (no functional protein is made). The mutation name means, that at position 2184 of the messenger RNA from which the CF-protein CFTR is read, there is an additional A. (A is one of the four components of nucleic acids that are shortened by A, G, C or T). Due to this additional component, it results a changing of the reading pattern: always 3 following nucleic acids of the messenger RNA are translated into an amino acid of the protein. The additional A at position 2184 is disturbing all, from here on the CFTR protein is built up wrongly and shortened. Several carriers of this mutation are known: 1994 an overview described already 5 carriers of this mutation.
The question is now, what this information can say about the expected course of the illness of your daughter.
In order to make clear conclusions, enough carriers of the mutation combination R352Q/2184insA have to be known - this is not possible due to the rarity of the variant R352Q. Also a rough classification in "mild" resp. "severe" mutation genotypes is based on the knowledge about the consequences of the mutation R352Q on the molecular level and that is at the moment not possible.
Specific drugs are therefore not available for both variants - for 2184insA there is actually nothing in development. Mutations with a change of the aminoacids ("missense mutations") like R352Q could be treatable by CFTR potentiators or CFTR correctors, this has however to be measured first and is actually part of research. In this article:
about 50 rare missense-mutation are investigated, R352Q is not under the tested. Only few of the tested missense-mutation are treatable with the there tested drug.
With my best wishes for the health of your daughter,
Frauke Stanke