Cystic fibrosis is an autosomal recessive condition caused by mutations in the CFTR gene i.e. both copies of the CFTR gene carry a pathogenic (disease-causing) mutation. Affected individuals experience over-production and subsequent stagnation of mucous in the digestive tract and respiratory system, leaving them at significantly elevated risk of severe infections which can be life-threatening.
Screening newborns for cystic fibrosis enables detection of the condition before symptoms present. This permits early therapeutic intervention (including dietary supplements, antibiotics and physiotherapy for effective management of symptoms) and can significantly improve an individuals’ long-term outlook.
The Yourgene® Cystic Fibrosis Lite assay is a simple and robust test which detects the 4 most common clinically relevant mutations in the CFTR gene (621+1G>T, F508del, G542X, & G551D) by PCR. It utilizes the same dried blood spot sample taken from the heel prick of a newborn.
In the NHS, Yourgene® Cystic Fibrosis Lite is used as part of a clinical pathway following upfront imunoreactive trypsinogen (IRT) testing. Active trypsin enzyme helps the body digest proteins in the gastrointestinal tract and is produced from the inactive proenzyme version, Trypsinogen. Excess mucous in the ducts between the site of synthesis (the pancreas) and the site of activation (the small intestine) can prevent Trypsinogen’s conversion to its activated form, resulting in an accumulation of Trypsinogen in the blood.
Since excess mucous production is one symptom of cystic fibrosis, elevated IRT in newborns is a potential indicator of the condition, but since other factors such as premature birth, or a stressful delivery can also cause raised IRT levels, confirmatory testing is required. When IRT levels are above the 99.5 centile (the top 0.5%), this is where PCR testing with the Yourgene® Cystic Fibrosis Lite kit comes in.
If two mutations are identified using the Yourgene® Cystic Fibrosis Lite kit (this can be the same mutation twice), the patient is given a presumptive diagnosis of cystic fibrosis. If only 1 mutation is identified then another kit, Yourgene® Cystic Fibrosis Base** (50 mutations), is used to look for a second mutation. If a second mutation is found, the patient is referred with a presumptive diagnosis of cystic fibrosis. If a second mutation is not found, a second dried blood spot sample is taken for further IRT testing. If no mutation is found using the Yourgene® Cystic Fibrosis Lite kit, then the report depends on the previously mentioned IRT levels. If IRT is <99.9 centile, then the report will say that cystic fibrosis is not expected. If IRT is >99.9 centile, then the report will say that there is a “high likelihood” of cystic fibrosis.
*Yourgene® Cystic Fibrosis Lite, previously known as Elucigene® CF4v2 Kit
***Yourgene® Cystic Fibrosis Base, previously known as Elucigene® CFEU2v1 Kit