Cystic Fibrosis

Question 1

How many individuals does cystic fibrosis affect?

Answer 1

Cystic fibrosis is a genetic disorder affecting around 1 in 2500 to 1 in 3500 individuals

However the disorder is far less frequent in African American and Asian American populations and can be as low as 1 in 31,000

Question 2

Mutations in what gene are responsible for cystic fibrosis?

Answer 2

Cystic fibrosis is caused by mutations in the CFTR gene encoding the cystic fibrosis transmembrane conductance regulator

Question 3

What is the key function of the CFTR protein?

Answer 3

The CFTR protein is responsible for the export of chloride ions out of epithelial cells which is essential in drawing water into the extracellular secretions and reducing their viscosity

Question 4

In what manner is cystic fibrosis inherited?
A) Autosomal Dominant
B) Autosomal Recessive
C) X linked Dominant
D) X linked Recessive

Answer 4

B) Cystic fibrosis is inherited in an autosomal recessive manner, meaning that an individual must receive two copies of a defective allele in order to show symptoms

Question 5

What is the most common mutation seen in over 90% of cystic fibrosis sufferers and how does this mutation cause disease

Answer 5

P508:

A deletion of a phenylalanine residue at position number 508 in the protein chain

The CFTR protein produced with this mutation is incorrectly folded in the endoplasmic reticulum and is subsequently degraded by the 26s proteasome

Question 6

How many classes of CFTR mutations are there:

Answer 6

There are 6 classes of CFTR mutations:

Classes I, II, III, IV, V, VI

Question 7

Which organs of the body are particularly affected by the accumulation of viscous mucus?

Answer 7

The lungs and the pancreas.

Accumulation of viscous mucus within the lung for example causes respiratory difficulties and accumulation in the pancreas impairs its ability to synthesise and secrete digestive enzymes into the digestive tract.

Question 8

Impaired functioning of the pancreas can also lead to what other condition?

(Hint. Blood glucose)

Answer 8

Impaired pancreatic functioning can also lead to diabetes mellitus as the secretion of insulin is impaired due to the accumulation of mucus in the pancreas

Question 9

Give examples of opportunistic microbes that can infect the lung of a CF sufferer?

Answer 9

Pseudomonas aeruginosa
Staphylococcus aureus
Haemophilus influenzae

Question 10

Which bacterium is responsible for the secretion of alginate within the lungs of CF sufferers, further exacerbating respiratory difficulties

Answer 10

Pseudomonas aueruginosa

Question 11

What main treatments are available for individuals with CF

Answer 11

Antibiotic therapies
Enzyme replacement therapies
Exercise
Bronchodilators

Question 12

Describe how the CF medication Ivacaftor works

Answer 12

Ivacaftor targets a defective isoform of the CFTR protein caused by the CF associated mutation G551D. G551D causes impaired channel opening in response to ATP. Ivacaftor facilitates greatly improved functioning of this channel, allowing more chloride transport out of the cells counteracting the effect of the G551D mutation