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Combination of DF508/R1162L

Ερώτηση
After testing I was found to carry the c.3485G>(R1162L) mutation and my husband the DF508 mutation, both in heterozygote. Does the combination of these two mutations cause CF, or any other pathology? Thank you in advance.
Απάντηση
Dear friend,
Your husband carries the DF508 CF mutation and you carry the R1162L CF mutation.
The CF gene is a large gene, which is located in the long leg of chromosome 7. It produces a protein, the CFTR protein, which is comprised of 1480 aminoacids and which can be found on the surface of the epithelial glands of exocrine glands. Its basic function is the normal functioning of chloride channels.
Up till now there have been more than 2000 CF mutations detected, the majority of which are pathological. This means that the production, or the function of the CFTR protein is affected. In the Greek population the most common mutation is the DF508, with a rate of 53,4%. 64 mutations have been found at a rate over 0.1%, and another 64 have been detected at a rate less than 0.1%, namely in one person.
For this reason a global datanbase, the CFTR2, has been established. It collects data afrom national registries and CF centers from all over the world for the clinical significance of the common CF mutations from 89052 patients. After the last data collection at 8/12/2017 the clinical importance of 374 mutation has been established.
312 mutations cause CF
36 mutations have variable clinical manifestations
13 mutations do not cause CF
13 mutations are of unknown clinical significance.

Based on these data the R1162L mutation does not cause CF.
Therefore, if you get pregnant, the baby will have a 25% chance to carry in heterozygone state the DF508 mutation, a 25% chance to carry in heterozygote state the R1162L mutation, a 25% chance to carry no mutation at all, and, finally, a 25% chance to carry both mutations (R1162L and DF508). In this last case the baby will not have CF, but it may present CFTR related disrease. CFTR -RD is a clinical entity that is associated with the dysfunction of the CFTR protein, but does not fulfill the diagnostic criteria of CF (Bombieri 2011).
The main clinical manifestations are congenital bilateral absence of the vas deferens in boys, recurrent of chronic pancreatitis and diffuse bronchiectasis in the adults.
Yours friendly,
Dr. Stavros Doudounakis

22.06.2018