Cystic Fibrosis (CF) has become the most common life-shortening hereditary genetic condition affecting 1 in 2500 live births in Caucasians. It is an autosomal recessive condition. Where the person has inherited two mutated alleles, they will display classic Cystic Fibrosis. Heterozygous carriers can display Cystic Fibrosis type diseases.
Cystic Fibrosis Transmembrane Receptor
Cystic Fibrosis (CF) is caused by a dysfunctional CF Transmembrane Receptor (CFTR). This receptor is encoded by the CFTR gene located on chromosome 7q31. The CFTR gene is composed of 27 exons, encoding 1480 amino acids. The CFTR receptor is responsible for Chloride ion flux out of cells and also regulates a number of other salt balancing receptors. Over 2000 mutations have been identified within the CFTR gene. The type of mutation is important for the treatment regime.
Routine testing for all possible mutations is neither feasible nor cost effective and is therefore confined to testing for the most common mutations. For example, the d508F mutation accounts for over 50% of CF cases worldwide. A targeted testing approach is most cost-effective, followed by secondary sequencing for confirmation.
CE-IVD products
Within defined geographical populations and ethnic groups, there are variations in the predominant mutations. To address this variation, Yourgene provides a range of CE-IVD products designed specifically for these populations and groups. The kits use Quantitative Fluorescence-Polymerase Chain Reaction (QF-PCR) technology and genetic analysers to detect point mutations, insertions or deletions in DNA.
Yourgene® Cystic Fibrosis Base is a pan-European CF testing kit designed specifically to address the most common mutations found across populations of European origin. Alongside this assay, Yourgene Health offer a number of population-specific bolt-on panels, as well as bespoke offerings for national programs. The assay is designed with all clinically relevant diagnostic scenarios in mind, including newborn screening and male factor infertility testing.
The Yourgene® Cystic Fibrosis Base assay identifies 50 mutations in total, and also analyses the intron 9 polyT tract with accurate measurement of the adjacent TG repeat. The polyT tract at the junction of intron 9 and exon 10 influences transcription. Specifically, the number of thymidine residues (5T, 7T or 9T) affects the splicing efficiency of exon 10. If the 5T allele is present, a proportion of exon 10 transcripts will be absent resulting in non-functional protein and variable CF symptoms. It is reported that the number of TG repeats upstream of the polythymidine tract can also influence splicing of exon 10. If present on the same allele as the 5T variant (cis) the larger the number of TG repeats, the higher the proportion of CFTR transcripts will lack exon 10. The CF range is unique amongst commercially available assays in its ability to accurately identify the number of TG repeats in addition to polyT status.
Tests
Yourgene® Cystic Fibrosis Base Lite
Yourgene® Cystic Fibrosis Base Lite
Detects the 4 most common mutations in the European population
Yourgene® Cystic Fibrosis Base
Yourgene® Cystic Fibrosis Base
Detects the 50 most common mutations in the European population
Yourgene® Cystic Fibrosis Base France
Yourgene® Cystic Fibrosis Base France
Detects the 29 most common mutations in the French population
Yourgene® Cystic Fibrosis Base Germany
Yourgene® Cystic Fibrosis Base Germany
Detects the 31 mutations outlined by the G-BA for newborn screening in Germany
Yourgene® Cystic Fibrosis Plus Italian
Yourgene® Cystic Fibrosis Plus Italian
Bolt on to Yourgene® Cystic Fibrosis Base to increase the mutation coverage for the Italian population
Yourgene® Cystic Fibrosis Plus Iberian
Yourgene® Cystic Fibrosis Plus Iberian
Bolt on to Yourgene® Cystic Fibrosis Base to increase the mutation coverage for the Iberian population
Yourgene® Cystic Fibrosis Plus UK
Yourgene® Cystic Fibrosis Plus UK
Bolt on to Yourgene® Cystic Fibrosis Base to increase the mutation coverage for the British population
Related products – Bundle with Yourgene’s Male Factor Infertility kit for complete male factor infertility investigation
Flexibility and simplicity from sample to report
Yourgene Health’s Cystic Fibrosis product range is compatible with most commonly employed DNA extraction protocols, thermal cyclers and capillary electrophoresis instruments. This flexibility in approach is complemented by simple and easy to use analysis software for reporting. Results can be analysed through either Life Technologies GeneMapper™ or SoftGenetics GeneMarker® software.
Fits comfortably into existing patient care pathways, with low DNA input volume
Target turn around time
Rapid workflow - DNA sample to result in <5 hours.
~30 mins total hands on time
Test Features
One PCR
- Two tube analysis
- Tube A: mutation detection and polyT status
- Tube B: wildtype detection
- Simple PCR set-up
- Reduced hands on time
One Analysis
- No post-PCR manipulation
- Compatible with ABI 3*** and SeqStudio Genetic Analysers
- Highly multiplexed 5 dye chemistry
- Rapid Analysis
One Report
- GeneMarker® and GeneMapper™ software applications
- Easy data review and analysis
- Informative single page reporting
- No data transfer required
Newborn Screening Clinical Pathway
Performance you can rely on
100% Accuracy, Repeatability & Reproducibility
Accuracy, Repeatability & Reproducibility
Accuracy was compared to Sanger sequencing. Accuracy of the Yourgene® Cystic Fibrosis Base (previously known as CF-EU2v1) assay was assessed by evaluating 159 samples representing a wide variety of CFTR gene variants from 4 separate sources.
View the full Your Comment articles below
Cystic Fibrosis Newborn Screening in the NHS - 1 June 2023
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 KitCystic Fibrosis Newborn Screening in the NHS – 1 June 2023
Related Publications
Bienvenu T, Lopez M, Girodon E. Molecular Diagnosis and Genetic Counseling of Cystic Fibrosis and Related Disorders: New Challenges. Genes. 2020 June 4.
Sadik I, Pérez de Algaba I, Jiménez R, Benito C, Blasco-Alonso J, Caro P, ... & Yahyaoui R. Int J Neonatal Screen. Initial Evaluation of Prospective and Parallel Assessments of Cystic Fibrosis Newborn Screening Protocols in Eastern Andalusia: IRT/IRT versus IRT/PAP/IRT. 2019 September 3.
Cystic Fibrosis Mutation Spectrum in North Macedonia: A Step Towards Personalized Therapy. Terzic M, Jakimovska M, Fustik S, Jakovska T, Sukarova-Stefanovska E, & Plaseska-Karanfilska D. Balkan Journal of Medical Genetics. 2019 August 28.
Petrova G, Yaneva N, Hrbková J, Libik M, Savov A, & Macek Jr M. Identification of 99% of CFTR gene mutations in Bulgarian-, Bulgarian Turk-, and Roma cystic fibrosis patients. Mol Genet Genomic Med. 2019 June 27.
Rueegg C.S, Kuehni C.E, Gallati S, Jurca M, Jung A, Casaulta C, … & Swiss Cystic Fibrosis Screening Group. Comparison of two sweat test systems for the diagnosis of cystic fibrosis in newborns. Pediatr. Pulmonol. 2019 January 4.
Marcão A, Barreto C, Pereira L, Vaz L. G, Cavaco J, Casimiro A, ... & Vilarinho L. Cystic Fibrosis Newborn Screening in Portugal: PAP Value in Populations with Stringent Rules for Genetic Studies. Int J Neonatal Screen. 2018 June 29.
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