Genotype Matters

Yesterday we launched 'Genotype Matters', allowing people with cystic fibrosis to learn more about their genotype, and how it is important in the era of personalised medicine. Dr Janet Allen, Director of Research & Care, has been overseeing the project at the Cystic Fibrosis Trust and here gives some background to it.


I am delighted to announce that we have launched our Genotype Matters campaign. We have been working with the CF centres in this area for a while. We ran a very successful pilot last year where we were able to pay for some of those whose genotype was unknown to have a blood test, and now we are able to extend the offer to all those who have a question mark about their genotype in the CF Registry. Cystic fibrosis is a clinical diagnosis made by expert CF specialists. In the past, the genotype information was provided afterwards and recorded in the CF Registry. However, the early genotyping panels only covered three or four common genotypes. As our knowledge of cystic fibrosis has increased, it has become clear that there are many different CF-causing mutations and not all of these are on the most recent standard test as they are very rare. So, we know that there are about 900 patients in the CF registry (out of just over 10,000) where the genotype record is missing for one or both genes (entered as ? or ??). In the past, knowing the exact genotype was not a high priority as treatment had nothing to do with knowing the genotype.

However, the picture changed with the appearance of ivacaftor (Kalydeco) which is prescribed for people who carry the G551D mutation. This is the first genotype-specific treatment and we anticipate that others will appear in the next few years that are targeted to other mutations. What’s more, it has become clear that ivacaftor (Kalydeco) can have beneficial effects on some people with a limited number of very rare mutations (so called non G551D gating mutations) and is already being used in the US for these very rare mutations. So it now becomes important that everyone wherever possible knows their genotype. Clearly, for the vast majority of people with CF this information is available and in their medical notes. We believe it is your right to know this information, and if you don’t we urge you to ask at your next clinic visit. If your doctor says the record in the registry says “?” or “??”, then we will cover the costs of the most up-to-date test that covers the rare genotypes. This is quite an expensive test so we are asking your doctor to double check with us and the CF Registry to make sure we don’t waste this opportunity.

In the pilot study, we found it was not always possible to identify the genotype even with the most modern test, because for technical reasons the test isn’t able to cover the entire gene. So our aim this year is that everyone with cystic fibrosis knows their genotype based on the most up-to-date test but recognise that for a small number of people this information will still remain unknown.

Why does this matter? Ivacaftor is the first of a new generation of treatments that help certain genotypes. However, even more exciting is the possibility to correct the mutation in the person’s own gene – so called genetic editing. For this, the precise genotype information is required. The approach works in the laboratory but as usual it will take some time before this lab-based work becomes reality.

You can find out about your genotype, or if you don't know it, learn how to get tested for it, at www.genotypematters.org