CAUSES AND
TRANSMISSION

Causes and transmission

Why are we born with cystic fibrosis?

Typically, a person has two normal copies of the CFTR (Cystic Fibrosis Transmembrane Regulator) gene. Individuals with cystic fibrosis, however, have two mutated copies of the CFTR gene, meaning the DNA sequence is altered. A healthy carrier has one mutated and one normal copy of the CFTR gene. Consequently, a child born with cystic fibrosis inherits two CFTR gene mutations in his genetic makeup, one from each parent. The parents each carry only one defective gene, do not show any symptoms of the disease, and are therefore considered healthy carriers of cystic fibrosis.

In Italy, approximately one in 30 people is a healthy carrier of cystic fibrosis. This means that about one in 900 couples consists of two carriers.

FFC Ricerca fibrosi cistica_riceratori laboratorio

At each pregnancy, two parents who carry the defective gene have:

  •  1 in 4 (25%) chance of having a child with CF. This happens when both pass on the defective gene;
  •  1 in 4 (25%) chance of having a child who is neither affected by nor a carrier of cystic fibrosis. This happens when neither of them passes on the defective gene;
  •  2 in 4 (50%) chances of having a healthy carrier child. This happens when only one of the two transmits the defective gene.

The CFTR gene, located on chromosome 7, contains the information to produce a protein responsible for regulating the transport of chloride and bicarbonate ions across epithelial cell membranes, which line both external and internal surfaces of many organs. Each person has two copies of chromosome 7 and, therefore, two copies of the CFTR gene.

Mutations in the gene lead to a production of a defective CFTR protein or even prevent its synthesis, resulting in water-deficient secretions which are thick and sticky (hence the former name for the condition “mucoviscidosis”, i.e. slimy mucus). It also entails a 4 to 5 times higher than normal concentration of salt in sweat. In the pancreas, stagnant secretions can form cysts, and the surrounding tissue tends to become inflamed, hardened, and fibrotic. Hence the name “cystic fibrosis”, which in full would be “cystic fibrosis of the pancreas”, despite the fact that the pancreas is only one of the affected organs. In 85-90% of cases, the pancreas does not perform its normal function of releasing enzymes into the intestine for food digestion. The organs with the most significant clinical consequences are the bronchi and lungs, where mucus tends to accumulate, making the patient prone to recurrent respiratory infections and progressive inflammation, eventually leading to respiratory failure. Other organs affected involve the nasal and paranasal cavities, the intestines, the liver and the male reproductive system.

OTHER INSIGHTS

HEALTHY CARRIES

THE CFTR GENE

MANIFESTATION AND EVOLUTION