Cystic Fibrosis Newborn Screening

Cystic fibrosis is a common autosomal recessive genetic disorder¹. This means that to have cystic fibrosis, a person must have inherited a defective gene from each of his or her parents². This gene is located on chromosome seven². Absence or mutation in this particular gene results in worse performance or absence of the Cystic Fibrosis Transmembrane Conductance Regulator². This is most commonly found in Europe, North America, and Australia¹. This gene manages anion transport and mucociliary clearance in the airways¹. With the failure of this function, the results are mucus retention and chronic infection in the lungs¹. Nowadays, modern technology provides aid for patients with their diseases and gives them a longer and more active life. Newborn screening for cystic fibrosis is a modern technological advance which is designed to detect early signs of cystic fibrosis.

Several methods under the name of the Newborn Screening are used to detect whether a newborn has cystic fibrosis or not¹. These methods include immunoreactive trypsinogen (IRT) testing combined with DNA mutation analysis and the sweat chloride test¹.

IRT stands for Immunoreactive Trypsinogen Test. The procedure of this test is a chemical reaction. Trypsinogen is made from the pancreas, and it normally transmits to the intestines where it is activated to a form of an enzyme called trypsin. In a patient who has cystic fibrosis, the thick mucus covers the pancreatic ducts¹. Therefore, trypsinogen won’t reach the intestines, and the amount of trypsinogen goes up. This test runs with a blood sample, and if the results come out with a normal level of trypsinogen, then this test is reliable, but if there is a high level of trypsinogen, then more tests need to be run to find out whether the patient has cystic fibrosis or not.

A sweat chloride test is the amount of chloride in patient’s sweat. In a patient that has Cystic Fibrosis, the sweat chloride test will result in significantly higher levels of chloride in sweat than a person that does not have cystic fibrosis due to the restricted movement of chloride.

The gene mutation test is a DNA sequencing test to locate a defective gene in the chromosome. There are many different types of mutations that can cause a deficiency in the production of the CFTR protein. More than 2000 CFTR variants have been discovered¹. About 15% of the identified gene variants are not associated with CF¹. CFTR mutations can be classified into six classes according to their effects on protein function¹. Classification is helpful because it relates to the molecular and cellular processes in gene translation and protein processing and has some useful clinical relations¹. Class I, II, and III mutations are associated with no residual CFTR function and patients with these mutations on average have a severe phenotype, whereas individuals with class IV, V, and VI mutations have some residual function of CFTR protein and have a mild lung phenotype and pancreatic deficiency¹. Today, different laboratories use a wide variety of panels depending on the patient’s need, like the twenty-three panel or panel of seventy. The following is an example of a molecular CF test.

Lab Corporation of America published a procedure for a Cystic Fibrosis molecular diagnostic³;

The coding sequence of CFTR is amplified by polymerase chain reaction and each PCR product (amplicon) then sequenced bi-directionally, using Sanger sequencing methodology.

CFTR	Chr7(q31,2)
Nucleotide Change	Amino Acid Change	Consequencing	Zygosity	Relation to Cystic Fibrosis
c.1327G>T	p.Asp443Tyr	missense mutation	homozygous	recessive, associated

1. Prof J Stuart Elbom, Cystic Fibrosis, Lancet, 19-25 November 2016, Volume 388, Issue 10059, page 2519-2531

3. Corporation of America Published Documents 2014 available @ http://oneworld.labcorp.com/Billing/TestMaster/Resource Center/Sample Reports/C-4/Cystic Fibrosis (CF) CFTR 252763.pdf

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