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R709X and V4SEA?

Is there any known info about the V4SEA mutation along with R709X?
Dear Questioner, thank you for your question.

The mutation R709X is a class-1-mutation where a so called single base substitution led to an early stop codon. This is also called nonsense-mutation. This type of mutation is expected to significantly disrupt CFTR protein production and result in little or no functional CFTR protein in the cell. Therefore, it is predicted that this mutation will cause CF.

The V4SEA is a mutation not currently listed on the CF mutations databases available. These rarer CF mutations are initially often not allocated to a specific class of mutation on CF Mutation databases. Furthermore, by virtue of being rare, it can also be challenging to be precise with regard to phenotype, or severity of disease, that the mutation renders in any given individual. In addition, 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.
Furthermore, 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.

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

Yours Sincerely

Katherine O’Neill Physiotherapist
Prof Stuart Elborn Consultant Physician

The answer is edited by: Prof Stuart Elborn