Lecture 4 Flashcards
What is cystic fibrosis?
Cystic fibrosis is a common autosomal recessive disease that affects chloride electrolyte metabolism and is associated with defects in several organs’ functioning.
How common is cystic fibrosis in Caucasians?
Cystic fibrosis affects 1/2500 births and 1/1500 in Ireland.
What is the diagnostic test for cystic fibrosis?
The chloride sweat test is used to diagnose cystic fibrosis. It involves collecting sweat from the skin, which is partly made of pilocarpine, and a mild electric current is applied. If children have a sweat chloride concentration of more than 60 mmol/L and 80 mmol/L in adults, they are diagnosed with cystic fibrosis.
How does cystic fibrosis affect the lungs?
Bronchioles progressively become dilated and inelastic due to mucous build up. The lungs come under constant attack from bacterial species such as Pseudomonas aeruginosas and Staphylococcus aureus. Over time, bacteria become resistance to antibiotics, and death frequently occurs through pneumonia or severe hemoptysis. The final treatment is often lung transplant, although physiotherapy can help offset the severity of symptoms.
What is the treatment for cystic fibrosis?
The treatment for cystic fibrosis includes nutritional repletion with pancreatic enzyme supplements, relief of airway obstruction by postural drainage, mechanical vests, recombinant DNase (Pulmozyme), treatment of airway infection with oral and intravenous antibiotics, suppression of inflammation with steroids or high-dose ibuprofen, and lung transplantation.
Where is the CF gene and what are the markers nearby?
The CF gene is located at 7q31 and has two flanking markers, Met and J3.11.
What is linkage disequilibrium?
Linkage disequilibrium is the nonrandom association of alleles at two or more loci that descend from single, ancestral chromosomes (regions that are IBD).
What is the cause of CF?
A defect in the chloride channel causes CF. CFTR controls the transport of sodium ions. If CFTR is not present, cilia don’t work, bacteria gather, WBCs are attracted, and mucous is formed on the airway surface.
What is the test for cystic fibrosis, and how many steps are there?
Cystic fibrosis is tested for in three steps: heel prick to screen for levels of immunoreactive trypsin levels in serum, followed by the sweat test, followed by the DNA test. Most tests screen for the 25 most common mutations (80-90% of Caucasians in the US).
What is the defect and treatment for Type 1 CFTR defect?
Stop codons, no protein made (G542X). Aminoglycoside antibiotics suppress premature stops by allowing incorporation of amino acid.
What is the defect and treatment for Type 2 CFTR defect?
Retention of mis-folded protein in ER, subsequently degraded (defective protein processing, DF508)
Chemical, molecular or pharmacological chaperones, to stabilise protein structure and protein folding
What is the defect and treatment for Type 3 CFTR defect?
Impaired channel opening (defective regulation, G551D).
CFTR activators
What is the defect and treatment for Type 4 CFTR defect?
Reduced concentration, impaired flow of ions (altered conduction of channel)
Increase overall cell surface content, or stimulate existing channels with potentiators
What is the defect and treatment for Type 5 and 6 CFTR defect?
Type 5 and 6: Reduction in mRNA or protein levels (otherwise normal) (A455E)
Splicing factors, potentiators
What do CF Type 1-3 patients usually have that Type 4-6 don’t?
pancreatic exocrine insufficiency and so develop CF related diabetes mellitus.
