Testing for hereditary mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene

Kessels, SJM, Morona, JK, Mittal, R, Vogan, A, Newton, S, Merlin, T
Record ID 32018000668
Original Title: Application 1216
Authors' results and conclusions: Safety - No studies on the safety of prenatal cystic fibrosis transmembrane conductance regulator (CFTR) testing were identified. Adverse events from change in management (termination of pregnancy (TOP))- Surgical TOP in the first trimester can lead to complications such as infection, cervical laceration (rare), incomplete evacuation, uterine perforation (rare), haemorrhage and problems with anaesthesia. Side effects and complications from pharmaceutical TOPs in the first trimester are bleeding (moderate to heavy), pain, nausea, vomiting and diarrhoea. No maternal deaths were reported from surgical or pharmaceutical TOP. Effectiveness - 1) Diagnostic accuracy - Overall, the sensitivity of CFTR mutation tests is high when detecting mutations included in the mutation panel. Both panel-based and exon-scanning CFTR mutation tests, as well as DNA sequencing-based tests, cannot detect large deletion or insertion mutations, which occur in about 2% of cystic fibrosis (CF) patients worldwide. In the case of a negative test result, it is important for the diagnostic laboratory to explain the scope of the mutation testing undertaken and the likelihood of the person being truly negative, particularly when one of the consequences of testing may be TOP. 2) Change in patient management (prenatal testing only) - In prospective patients who are known carriers, a positive CFTR test in the fetus led to TOP in 155/163 cases (95%). This shows that CFTR mutation testing does change management and that a positive test result predicts TOP. It is assumed that no TOP would occur in the absence of prenatal testing. 3) Treatment effectiveness - One key result of prenatal CFTR mutation testing is that fewer children with CF will be born. Conclusion - It is suggested that, relative to no genetic testing and subsequent clinical diagnosis after birth, prenatal CFTR mutation testing is likely to correctly identify most CFTR mutations if the appropriate test is used, and will result in the termination of a majority of the affected pregnancies. CFTR mutation testing reduces the frequency of people being born with CF. The test has inferior safety compared with clinical diagnosis after birth, due to the risk of miscarriage associated with prenatal sampling procedures and the adverse events associated with TOP. There was insufficient evidence to make a direct comparison between the psychological impact of TOP and the impact of raising a child with CF, although in the short term the rates of depression appear to be similar.
Project Status: Completed
Year Published: 2015
English language abstract: An English language summary is available
Publication Type: Not Assigned
Country: Australia
MeSH Terms
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Cystic Fibrosis
Organisation Name: Adelaide Health Technology Assessment
Contact Address: School of Public Health, Mail Drop 545, University of Adelaide, Adelaide SA 5005, AUSTRALIA, Tel: +61 8 8313 4617
Contact Name: ahta@adelaide.edu.au
Contact Email: ahta@adelaide.edu.au
Copyright: Adelaide Health Technology Assessment (AHTA)
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