Parents - carriers of CF mutations

Question

Good morning,

I am at the 12th week of gestation with my second child, and my doctor recommended to check for CF, something my gynecologist had not recommended during my first pregnancy. I was checked for 85% of the CFTR mutations and I was found to carry the G542X mutation. My husband was tested for 100% of the mutations and he was found to carry in heterozygotic the mutations F1052V and G1069R in exon 17b. We will do a trophoblast test in a few days. What really worries me is my son. He is 2 years and 3 months old. He is healthy, with no problems and excellent growth. Everybody thinks he is older. He received an IRT test when he was born, and it was negative. My pediatrician tells me not to worry. What do you believe? Thank you!

Answer

Dear friend,
You are at the 12th gestation week of your second pregnancy and you carry the G542X CF mutation. You husband carries two mutations of variable clinical expression (F1052V and G1069R).

The chances for the fetus to carry the mutation G542X, in combination with either of your husband’s mutations, is 50%. Regarding the fetus, where a trophoblast examination must be performed, the most severe combination will be the one of G542X with either one of your husband’s mutations. In this case it will be a mild case of CF with pancreatic sufficiency.

The other 50% will mean that the fetus will carry one of your husband’s mutations. You also have a boy, 2 years and 3 months old. He has not presented any particular problem from the respiratory, or the peptic system, and his IRT check as a neonate was negative (I would like to know the exact value). I AM NOT concerned about your son, however, a sweat test, or a genotype test will confirm my opinion.

A person with CF carries two abnormal mutations. These variants are classified in four categories:
1. Mutations that cause CF
2. Mutations without clinical significance
3. Mutations of variable clinical expression
4. Mutations of unknown clinical significance
(Castelani, Journal of Cystic Fibrosis 2008, 179-96).

I am curious about your husband’s health status. Has he ever had problems with his respiratory, or peptic system, or does he have a history of pancreatitis, or nasal polyps?

Yours friendly,
Dr. Stavros Doudounakis

15.05.2017