508 r117h T5

Question

My grandson has recently been diagnosed with CF.
His details are 508 and r117h T5. Sweat test 47.

What cf symptoms will develop?

Also - what medication will be available in the near future which may address the symptoms?

Thank You

Answer

Dear questionner

Thank you for your question regarding your grandson.

The impact that any given CF mutation has on severity of disease is often determined by the combination of CF mutations, rather than any one mutation in isolation.[1]
Besides, 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.

Worldwide, Del F508 is the most prevalent CF causing mutation. The R117H mutation is a special mutation. It can cause a mild kind of CF. Typical for mild mutations is indeed that patients have normal digestion, only mild lung or sinus problems, but possibly problems with male fertility due to absence of the vas deferens. The factors that determine whether R117H provokes the disease or not are not fully understood. However it has been found that the T tract influences disease severity: mainly subjects who carry T5 on the R117H allele have a higher risk of developing lung disease.
If you are planning to get genetic counseling, you will get even more detailed information on this topic.

Regarding treatments, your CF health care team will decide on current treatments based on your grandson’s current health and any symptoms he might present with. These may come in the form of oral or nebulised antibiotics, nebulised mucolytics (solutions which help thin any secretions in the lungs), inhalers and airways clearance techniques (breathing techniques to help keep the airways free from excess secretions). You will also receive advice on your grandsons diet and oral enzymes (if he is pancreatic insufficient).

New therapies which treat the defect causing CF, termed “small molecule therapies” are currently being tested in patients with different mutations, in clinical trials. Ivacaftor or Kalydeco is one such therapy that is now approved for use in patients with the mutation G551D.
However, the pharmaceutical company Vertex is currently running a study, treating patients with a R117H mutation with Ivacaftor. The results from this study are expected early next year [2].

I hope you find this information helpful.

Best wishes

Katherine O’Neill


References

1.Comer, D.M., et al., Clinical phenotype of cystic fibrosis patients with the G551D mutation. QJM, 2009. 102(11): p. 793-8.

2. investors.vrtx.com/releasedetail.cfm?ReleaseID=798106

01.12.2013

The answer is edited by: Katherine O'Neill