Genetic Disease: Cystic Fibrosis (CF)

Genetic Disease: Cystic Fibrosis (CF)

Dr R K Patel

INTRODUCTION: Cystic fibrosis is an inherited Autosomal recessive monogenic genetic disease in humans. The disease characterized by the accumulation of thick and sticky mucus that can damage many body organs starting with respiratory system associated with chronic digestive system.  Mucus is a substance that protects the linings of the respiratory system, digestive system, reproductive system, and other organs and tissues.  Mucus is a viscous fluid containing inorganic salts, glycoproteins, antimicrobial enzymes, immunoglobulins and water and produced from cells found in  mucous glands.  In cystic fibrosis, the body produces mucus, which is abnormally thick and sticky. This abnormal mucus can block the windpipe of the respiratory system and can lead to severe breathing problems and bacterial infections in the lungs. Over time, mucus and infections result in permanent lung damage, including formation fibrosis and cysts in the lungs. Cystic fibrosis is a fatal disorder of childhood. Whereas, with improved treatments and better management many people with cystic fibrosis now live well into adulthood. The Cystic Fibrosis Foundation (CFF) is projecting a life expectancy of 37 years for CF patients currently. Whereas a UK study predicts that a CF patient can expect to live more than 50 years of age. In countries with limited resources like India, the survival of children with CF is lagging behind considerably as compare to the developed countries.

Autosomal recessive inheritance

Whena fathercarrier of CF mates with normal mother will produce 50% carrier and 50% normal progeny (figure 1). Similarly, when both father and mother are carrier, they will produce 25% normal, 50% carrier and 25% affected for CF (Figure 2).

SYMPTOMS: the major symptoms are as under:

  1.  Affected babies have a blockage intestine that occurs shortly after birth.
  2.  Persons have salty skin.
  3. Affected person suffers from persistent cough with phlegm.

 iv)     Frequent lung infections that include pneumonia or bronchitis.

  •  Wheezing or shortness of breath.
  •  Pain in abdomen, diarrhoea, heartburn, severe constipation, etc. are common gastrointestinal problems
  • Poor growth and less weight gain in spite of a good appetite and food intake.
  •  Frequent greasy and bulky stools with difficult bowel movements.
  • It affects male fertility as most people have congenital bilateral, absence of the vas deferens (CBAVD) or blocked vas deferens, which carry sperm.
  • It damages the pancreas and thus insulin production.


Cystic fibrosis is a common genetic disease within the white population in the United States. The disease occurs in 1 in 2,500 to 3,500 white newborns.  Cystic fibrosis is less common in other ethnic groups, affecting about 1 in 17,000 African Americans, 1 in 31,000 Asian Americans, 1 in 17000 American black population and 1 80000 in Native American population. Earlier, it was thought that the disease does not exist in India but the first case reported in 1968. Thereafter, there were reports of CF from all parts of India. The number of children born every year with CF may be about 10908 presuming incidence to be about 1 in 2500 live births; 2727 with a presumed incidence of 1 in 10000; and 681 with a presumed incidence of 1 in 40000  in India.


Cystic fibrosis transmembrane conductance regulator (CFTR) gene located on human chromosome 7 on with specific location 7q31.2. Normally, the CFTR gene provides instructions for making a protein called the cystic fibrosis transmembrane conductance regulator. This protein controls the movement of salt and water in and out of human body’s cells. CFTR is an ion channel protein that transports chloride ions across the membranes of cells that line airways, glands, and the digestive tract. Chloride ions balance the water, making mucus thick or thin (Figure 3). When Chloride ions do not pass through due to absence of CFTR membrane protein, the mucus viscosity becomes thick, which cannot be move by the epithelium cell cilia. The thick mucus attracts invading pathogens which becomes a layer over mucus and develops infection. Because of bacteria on mucus neutrophils comes out and neutralize the invading pathogen resulting in more and more thicker layer of mucus that causes a narrow passage of the airways, glands, digestive system etc. When it happens in exocrine gland pancreas it develops fibrosis and cyst.  

More than 1,000 mutations in the CFTR gene have been identified in people with cystic fibrosis. Currently, there are 1997 mutations listed in the CFTR mutation database. Most of these mutations change amino acids in the CFTR protein or delete a small amount of DNA from the CFTR gene. The most common mutation, called delta F508, is a deletion of one amino acid (phenylalanine in the tenth exon) at position 508 in the CFTR protein causing frame shifting. The delta F508 (ΔF508) constitutes about 70% of the total cases worldwide.  As a result of ΔF508 mutation in the CFTR gene, it produces abnormal channel of CFTR protein, which breaks down shortly after it is synthesized, so it never reaches the cell membrane to transport chloride ions. The mucus becomes thick because of less water and no ions transportation in and out of the cell membrane. The normal allelic variant of this gene is about 250,000 base pairs long with 27 exons. The product of this gene, CFTR protein, is made of 1480 amino acids and is a member of the ATP Binding Cassette (ABC) transporter super family.

Diagnosis of CF

Sweat chloride test reveals the greater chloride value (>60 mmol/L) than normal and baby skin tastes salty when kisses. Chest X-rays indicate inflated lungs, fibrosis in lung and scaring. A sinus X-ray shows the signs of sinusitis. Similarly lung function test, sputum culture can also help in the diagnosis. A blood test of a baby to estimate the levels of a chemical produced by the pancreas called immunoreactive trypsinogen (IRT).

Genetic test is the appropriate to detect mutation in the CFTR gene. As mutations are large in number in CFTR gene, it is advisable for PCR and DNA sequencing, and full mutation scan of the gene. The screening test for people without a family history of CF will also be done on the most common gene mutations, and so cannot be said to be 100% accurate.

Treatments and management for cystic fibrosis
Presently, there is no cure of cystic fibrosis but treatments are available to manage the symptoms, prevent complications, and make the condition easier to live with. The treatments include following:
  1. antibiotics treatment to prevent and treat chest infections
  2. medicines are given to make mucus in the lungs thinner and easier to cough up
  3. medicines are given to dilate the airways and reduce inflammation
  4. Clear the mucus of the lungs by special techniques and devices
  5. medicines are given to patients so that they can absorb food better for digestion
  6. Special diet and food supplements are provided to prevent malnutrition
  7. A lung transplant may be required if the lungs are damaged.
Figure – 1