Hello

Question

I have one-year-old boy diagnosed with cystic fibrosis at 6 months. We did the genetic test and the result was: M - G 542X heterozygous; 9T. Child‘s doctor says that the outcome would be a milder disease and he does not believe he will have major problems in the future. But another doctor said that whatever the result is this disease is severe.
What is exactly this outcome?

Answer

Hello,
I understand from your question, that the child has a single mutation G542X, the second could not be detected, either because the kit couldn’t detect the mutation, or the child is just a carrier. But if the child has typical clinical symptoms, associated with the detection of a mutation, then the second mutation probably exists but it has not been detected. For intron 8, allele 9T is present, you did not say if it’s a 9T/9T genotype or another variant, only the information of 9T is given. 9T allele is not associated with the disease, only 5T allele may be associated with CF.
The answer was edited with Dr Liviu Tamas`s help, specialist in cystic fibrosis genetics.

Mutations can be classified as severe (class I, II, III, G542X belongs to those kind of mutations) and milder ones (class IV,V). Each CF patient has two mutations (one on each chromosome inherited from his father and his mother) on the CFTR gene locus, and the clinical picture is determined by the milder mutation of both. So in case of your child, we have one severe mutation, namely G 542X, however we do not know anything about the other one; if it would belong to the mild mutational classes the clinical picture would be less severe, compared to the case, that the second mutation would also be a severe one. Therefore, one cannot make a statement unless the second mutation is known.

Regarding genotype-phenotype correlation, in general, it does not apply equally to all patients, not all patients with the same genotype (mutations) have the same clinical picture nor the same trend.
Ragards,
Prof.Dr Liviu Pop and Dr. Tamas

15.09.2014