Module 8/9 - Mutations and human disease ~ further study

Question 1

What is cystic fibrosis?

Answer 1

A disease in which mucus builds up in the lungs, causing pulmonary issues, and in the pancreas, causing digestive issues.

Question 2

What are the symptoms of cystic fibrosis?

Answer 2

• Recurring chest infections
• Wheezing, coughing, shortness of breath and damage to the airways (bronchiectasis)
• Difficulty putting on weight and growing
• Yellowing of the skin and the whites of the eyes (jaundice)
• Diarrhoea, constipation, or large, smelly faeces
• A bowel obstruction in newborn babies (meconium ileus) – surgery may be needed

Question 3

How is cystic fibrosis diagnosed?

Answer 3

Newborn babies are given a heel prick test which tests their blood and indicates whether they may have CF

If the results show there is a possibility, then there is a sweat test (testing if salt sweat is excessive) and a genetic test (seeing where it came from)

Question 4

Treatment for cystic fibrosis?

Answer 4

Various lung medicines and physical exercise to clear the mucus

Question 5

The five classes of CF gene mutation?

Answer 5

1) Protein production mutations
2) Protein processing mutations
3) Gating mutations
4) Conduction mutations
5) Insufficient protein mutations

Question 6

Protein production mutations: what are they

Answer 6

Include nonsense and splice mutations, interfere with the production of the CFTR protein

Question 7

Protein processing mutations: what are they, how are they formed, and what treatments are there?

Answer 7

When the CFTR protein cannot properly form its correct 3-D shape and function.

When a mutation causes an amino acid to be deleted (F508del) or an incorrect amino acid to be added ()

The drug combination Trikafta® (elexacaftor / tezacaftor / ivacaftor) works by enabling CFTR protein with an F508del mutation to fold in a correct shape and then activates the protein to allow more chloride to pass through

Although this drug combination is not a perfect fix, it helps the mutant CFTR protein to move some chloride, reducing the symptoms of CF

Question 8

Gating mutations: what are they and what are the treatments?

Answer 8

Gating mutations lock the gate in the closed position so that chloride cannot get through

The drug Kalydeco® (ivacaftor) helps people with gating mutations by forcing the gate on the CFTR channel to stay open

This enables chloride to move through the channel and reduces the symptoms of CF

Question 9

Conduction mutations: what are they?

Answer 9

Some mutations change the shape of the inside of the channel so that chloride cannot move through as easily as it should

Question 10

Insufficient protein mutations: what are they and what are the treatments?

Answer 10

Not enough CFTR protein is synthesised

Ivacaftor in both Kalydeco and Symdeko can force the gate on the normal CFTR protein to stay open, allowing higher chloride flow through the channel,
compensating for the insufficient protein numbers on the surface of the cell.