Non pathogenic polymorphisms

Question

My husband was tested for 89& of the CF mutations and no pathogenic mutation was detected. However, three non pathogenic polymorphisms were detected. Why are they in the report, since they do not cause CF? What is their role?

Answer

Dear friend!
The term mutation refers to the molecular alteration in the DNA sequence of a gene (its structure changes). Based on this definition the possible effect of the mutation on the gene function is not clarified. This effect can be neutral, detrimental or beneficial.
The term polymorphism refers to the alteration of the DNA sequence (i.e. the order of its components changes, not the components themselves), an alteration that has a frequency of at least 1% in the general population. Given the high frequency of the polymorphism the opinion was that they did not have any clinical consequences. This is clearly not the case, since there are several polymorphisms in the CFTR gene that affect the severity of the disease. What matters is which polymorphism is combined with which mutation for the diagnosis and the prognosis of the disease (Castellani et al 2008).
A polymorphism, or a mutation, on their own, cannot cause any type of CF. Two mutations (one in each gene, not in the same one), or one mutation and one polymorphism (one in each gene, not in the same one) must be combined, in order for the disease to manifest.
Yours friendly,
Dr. Stavros Doudounakis

11.12.2015