Μutation combined with polymorphism

Question

I am 14 weeks pregnant and I have a 4 year old son. During the genetic testing I was examined for 90% of the CF mutations and I was found to carry: c.1584+12T>C (rs193922502), along with the non pathological polymorphisms p.V470M (rs213950,c.1408G>A). My husband was detected to carry the c.1522_1524delTTT (p.Phe508del), rs121909001. The examined sample carried the genotype Τ9/Τ7 & TG10/TG11 in regard to the gene regions T & TG. What are the chances that the fetus will have CF in a severe or mild type, or present other problems (it is male). What about my son? (He is perfectly healthy, has never received antibiotics, but is not tested for CF). Thank you, A.

Answer

Dear A.,
There is a 75% chance that the fetus will carry one or no CF mutation and be perfectly healthy.
There is, however, a 25% chance that the fetus will carry two mutations, the
DF508/1584+12T>C. The DF508 mutation is the most common typical CF mutation. About the second one (legacy name 1716 A/T) in a clinical database for CFTR mutations with 40000 registered CF patients there is no report about it. There are reports of this mutation being combined with pancreatitis (Casals et al. 2004), as well as reports of it being combined with mild, atypical CF cases.
A child with the 1716 mutation will not present the typical clinical symptoms of CF, and often the diagnosis is made at a late age due to male sterility, pancreatitis or dehydration.
Yours friendly,
Dr. Stavros Doudounakis

12.06.2015