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F1052V and F508del

We are expectant and near 14 weeks gestation. My wife carries F508del and I carry F1052V. The results of our CVS test were revealed that the baby inherited both faulty genes. We would like to know what to expect in clinical manifestations? What treatments might be available? Should we bank the cord blood? But mainly, what degree of CF might be presented.
Thank you in advance.
Thank you for your question.
F1052v is a mutation which can cause CF having been reported for the first time in a 1992. This was in a male individual, and, akin to your child, had F508del on the other allele. In addition, he also had the I918M mutation in cis, in other words, on the same allele, as F1052v. His CF was diagnosed at the age of 29 and he had rhinosinusitis ( This report would suggest that this particular combination of mutations confers a mild form of disease, or a mild phenotype. We also know that although the F1052v mutation renders some degree of loss biosynthetic processing of CFTR function, this is not quite as marked as for the F508del mutation. This fact almost certainly explains why CF people with this mutation have a milder phenotype (often with pancreatic sufficiency and not so requiring enzyme supplementation). This probably can be explained as partial activity of CFTR at the cell membrane is maintained.[1]
F1052v is considered a rare CF mutation. These rarer CF mutations are initially often not allocated to a specific class of mutation on CF Mutation databases. Furthermore, by virtue of being rare, it can also be challenging to be precise with regard to phenotype, or severity of disease, that the mutation renders in any given individual. In addition, and perhaps to complicate matters further, the impact that any given CF mutation has on severity of disease is often determined by the combination of CF mutations, rather than any one mutation in isolation.[2]
Finally, it is important to keep in mind that there is a high variability in phenotype within identical CFTR genotypes.[3] As a definite modifier genes remains to be identified we support consensus statements advising that clinicians should not use genotype alone to predict clinical outcomes at the time of diagnosis.[4]
The treatments available for patients with CF, in very general terms, are similar regardless of the underlying combinations of mutations. The goals of these therapies are, in essence, to alleviate symptoms, mitigate the progression of disease, avoid complications, and by doing so, attempt to improve the overall quality of life for the patient. These treatments and approaches include antibiotics, anti-inflammatory drugs, enzymes, mucolytics, airway clearance techniques, dietary advice, appropriate exercise and, for those individuals who progress to severe lung damage, lung transplantation. The CF Trust Website has information about the symptoms and treatments of CF, and is informative in terms of the various challenges CF patients may be confronted with during their day to day lives.[5]

Dr David Comer

Reference List

1.Cotten, J.F., et al., Effect of cystic fibrosis-associated mutations in the fourth intracellular loop of cystic fibrosis transmembrane conductance regulator. J Biol Chem, 1996. 271(35): p. 21279-84.
2.Comer, D.M., et al., Clinical phenotype of cystic fibrosis patients with the G551D mutation. QJM, 2009. 102(11): p. 793-8.
3.Loubieres, Y., et al., Association between genetically determined pancreatic status and lung disease in adult cystic fibrosis patients. Chest, 2002. 121(1): p. 73-80.
4.Castellani, C., et al., Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. J Cyst Fibros, 2008. 7(3): p. 179-96.