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Screening for Cystic Fibrosis

Screening is the process of testing for a disease or health risk before it has caused a health problem. For a genetic disease like CF, this includes testing for carrier status.

Cascade screening

Cascade screening is the term used for identifying carriers of a disease-causing mutation (such as those that cause CF). It occurs after the identification of an affected individual and the consequent genetic counselling of the family. The siblings of the affected individual and his/her parents can be screened for the presence of the mutation(s) identified in that family. Those who are carriers are then counselled about the implications and the tests that can be done on their partner. It is important that screening of siblings should only be done when the sibling is able to understand the implications of the test result i.e. capacity for consent must be assessed before the test is done. Generally this is best postponed to 18 years unless the sibling is sexually active.

When a mutation in a family is known, testing for the specific mutation can be offered. A negative result will exclude carrier status. A positive result confirms carrier status. The partner of a carrier (without a family history) can then be tested for the presence of a mutation. In this situation, a negative result does not exclude a carrier status, but can dramatically reduce the chance that it is present. A positive result confirms carrier status and allows the couple to make informed reproductive choices. The choices are the same as those that face the parents of an affected child. Genetic counselling is essential to allow such couples to make informed choices.

Newborn screening

The purpose of newborn screening is to identify an infant who is at increased risk of having CF. Importantly, this screening test process is not a diagnostic test. A positive screening test must be followed up with a diagnostic test before a diagnosis of CF is made and treatment commenced for those infants who require it. No screening test is perfect and all yield a proportion of false positive results (i.e. test is positive but the infant does not have CF) and false negative results (i.e. the test is negative but the infant does have CF; the opportunity for early treatment is missed).

All CF newborn screening is based on blood immunoreactive trypsin (IRT) and CFTR mutation analysis. Cascade screening and antenatal testing of carrier couples is possible and available in South Africa. Broad-based population newborn screening for CF is being investigated, but it is not practical at present. Newborn screening using testing strategies of uncertain validity is available in some private laboratories in South Africa.

The following references can be consulted should more detail about strategies and other aspects of screening is desired. Reference: Wagener JS, Zemanick ET, Sontag MK. Newborn screening for cystic fibrosis. Curr Opin Pediatr 2012;24(3):329-35

Potential future drugs for CF treatment based on genetic mutations

There is no cure for CF, but progress is being made on the development of drugs that are aimed at CF individuals with defined mutations in the CF gene. As a result of increased knowledge of the consequences of some of the mutations at the cellular level, these drugs are being developed and trials are taking place in selected CF Clinics abroad.

The first drug for CF, targeted at individuals with a specific CF mutation, was approved by the US Federal Drug Administration (FDA) in January 2012. Kalydeco (previously known as VX-770) is approved for use in CF patients with the D551G mutation and who are over 6 years old. Another drug, Ataluren (previously known as PTC124A) is currently in the trial phase. It is targeted at mutations called premature stop mutations or nonsense mutations, and include W1282X, G542X, R1162X, E69X and W1262X. These mutations are, however, relatively rare and will 16 only be appropriate for a small group of CF patients. Phase 2 clinical trials combining Kalydeco (previously VX-770) & VX-809 in patients with at least 1 Delta F508 mutation are well underway & promising interim results were demonstrated in April 2012. Should this combination be successful, it would be suitable for the treatment of a significant proportion of CF patients.

The developments in mutation-targeted therapy highlight the need to identify the DNA mutations in CF patients in order to assess whether they would be suitable
candidates for future treatments. For up to date information, visit the UK CF Trust website ( or the US CF Foundation website (