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DNA test/risk of passing CF on to children


me and my wife plan to have children. As a CF causing mutation has already been detected in my DNA, is there a high risk that our children will come down with CF? My wife was born on the Philipinnes, I am European, and it is very hard to find information regarding the relevant mutation that should be analyzed in her DNA - does it make sense to check her whole CTFR gene?
Thanks from Austria

Dear Thomas,
Generally, it can be said, that if you have been tested positive for one CF mutation, and your wife is not tested at all the risk of having a child with CF depends in the frequency of carriers (like you are one) in the general population. For people with European origin, a carrier frequency of 1/30 is assumed, however, even within Europe, this frequency varies broadly from 1/20 to 1/80 (CF is more frequent in the Northwest, prevalence goes down when coming to the Southeast of Europe). [1]
With an assumed carrier frequency of 1/30, your wife has the chance of 1/30 also to have one CF mutation in a pair of chromosomes, and you both have the risk of ½ to pass the CF mutation that is only on one of your paired chromosomes to the future child. Therefore the risk for you as a couple if your wife stays untested would be : ½ x ½ x 1/30 = 1/120.
However, your wife is not of Caucasian origin; I did not find any data about the carrier frequency in Asia directly, but there is data about the carrier frequency among Asian-Americans, that is about 1/90, so the risk decreases to : ½ x ½ x 1/90 = 1/360.
If one partner is positive for a CF mutation, it is advisable also to test the partner for CF mutations, then one can nearly exclude the risk (only “nearly” because there is not test, that finds all possible CF mutations) or, in case the partner carriers also one mutation, to specify the risk for a CF child to ½ x ½ = ¼.
The standard genetic test kits test for 23-60 of the known 1800 CF mutations, having a mutation detection rate of 70-90%. This is of course dependent on the chosen mutations within this test kits; a standard European test kit tests for the most frequent European mutations, if it is used for an Asian person, the mutation detection rate will be markedly lower. However, the most frequent mutations for a certain population are known [2] and the mutation panel for testing of an Asian person should be adapted accordingly. It should include the most frequent ones for this population [2]. Therefore I would recommend to get in contact with a human genetics specialist and to discuss the problem that the European test kits will probably not be suitable for your wife. He can get in contact with the laboratory performing those tests, in order to initiate an investigation, testing a mutation panel adapted to the Asia origin of your wife. If this should not be possible, it still remains the possibility of doing a complete gene sequencing.
It remains of course your decision, how much security you would like to have in order to exclude the possibility of having a child with CF.
Hope this helps a bit,
Yours sincerely,
Dr. Daniela d’Alquen (Coordinator of the Central English Archive of ECORN-CF)

1 Castellani et al. in the Journal of Cystic Fibrosis 2010, 9:165-178: “Benchmarks for Cystic Fibrosis carrier screening: A European consensus document.”
2 Castellani et al in the Journal of Cystic Fibrosis 7 (2008) 179-196: "Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice"