Rare CF mutation risks?

Question

What is the risk for a white British male having a rare mutated CF gene? The 50 most common have been tested for and have come back as clear for mutations.

I have recently been found to be a carrier of a common mutation following blood tests after my baby was diagnosed as having an echogenic bowel at 20 weeks gestation. As a result my baby has been given a 1/20 chance of having CF. My partner's blood sample is being further tested for rarer mutations. I would like an idea of how likely it is my partner is a carrier of a rare mutation.

If my baby's echogenic bowel is gone at our next scan will his risk of having CF decrease also or stay at 1/20 because it was seen at 20 weeks?

Answer

Dear Questioner,

Thank you for your question.
The purpose of this forum is not to confirm or exclude specific diagnoses. For individual medical advice please continue to consult with your pediatrician or doctor. We can however give you some general information.
Over two million people in the UK carry the faulty gene that causes Cystic Fibrosis - around 1 in 25 of the population. Your husband has a 1 in 25 chance of carrying a faulty gene that causes CF.
Everyone has two copies of the CF gene: one inherited from the mother and one from the father. CF occurs when both copies of the inherited cystic fibrosis transmembrane receptor (CFTR) gene are mutated or altered. Scientists know more than one almost two thousand types of mutations in the CFTR gene, and new mutations are still being found. Most of these mutations are rare and worldwide, fewer than 20 mutations occur more frequently than 0.1%. The finding of only one mutation or no mutations does not exclude the diagnosis, but it makes it less probable. If both parents are a carrier, the baby has a one in four chance of being born with CF. A baby must inherit both mutated genes to be born with CF.
You baby's echogenic bowel at 20 weeks gestation, along with your blood results showing you to be a carrier of a common mutation have contributed towards the suspicion of your baby having CF. Concerning the number of 1/20 being the given chance for your baby of having CF, I do not really understand how this result came about.
In your case, the following calculation could be adequate:
You are known to be a carrier of one CF-mutation. So first of all the chance, that you pass this mutation to your baby, is 1/2. The probability, that your partner is also a carrier (without doing any test) is 1/25, and in order that your child will suffer from CF, he has to pass the mutated gene to the child, which again has the chance of 1/2. So, in summary, if your partner was not tested, the risk for you both to have a child with CF would be: (½) x (½ x1/25) = 1/100.
If your partner has been tested for 90% of the most common mutations with a test, we have a probability of 10% that he is still a carrier, so chance that your partner still is a CF carrier even with a negative result is 1/25 x 10/100 = 1/250.
In that case, there is 1 chance out of 2 that your partner will pass through his mutant CFTR gene to his child. The combined probability of a CF child for you and your partner is (½) x (½ x 1/250) = 1/1000.
So the negative test result of your partner reduced the risk from 1/100 to 1/1000 for you both to have a child with CF (compared with the overall risk of the general population to get a child with CF of 1/2500).
Further tests are carried out on the birth of the baby. The test is a heel-prick to sample blood as part of the normal Guthrie test carried out on all children. Other tests for Cystic Fibrosis are the sweat test (people with CF have more salt in their sweat, which can be detected) or a genetic test, which is a swab taken by gently rubbing the inside of the cheek to check for the faulty CF gene. Please continue to consult with your pediatrician and a genetic counsellor, who will help you with better planning for the birth in a hospital with neonatal intensive care facilities.


References:

• https://www.cysticfibrosis.org.uk /aboutcf/whatiscf/howdiagnosed/
•www.cftr2.org/index.php


Yours Sincerely

Katherine O’Neill Physiotherapist
Prof Stuart Elborn Consultant Physician
Dr. Daniela d'Alquen Pediatrician

24.01.2013

The answer is edited by: Prof Stuart Elborn