Cystic Fibrosis

1
Cystic Fibrosis

• Research By Felix Ratjen and Gerd DoringThe
  Lancet February 22, 2003
• Presented by

2
Introduction

• commonly known as CF
• most common autosomal recessive disorder in
  whites
• about 1 in 2500 live births
• CFTR- mutated gene
• discovery aided in diagnosis and showed its
  complexity
• better treatments have increased life expectancy
  for patients over the past decades

3
Focus

• Advances in treatments and understanding of
  cystic fibrosis
• Focus on pulmonary disease
• Accountants for most morbidity and deaths

4
Causes

• CF is caused by mutations in a 230 k gene on
  chromosome 7 encoding a 1480 amino acid
  polypeptide
• CFTR functions as a chloride channel in
  epithelial membranes
• there is over 1,000 mutations described so far

5
Mutations(CFTR)

• Can be grouped into 6 classes
• 1. CFTR is not synthesized
• 2. Defective processing
• 3. Regulation
• 4. Conductance
• 5. Partly defective production or
• processing
• 6. Defective regulation of other channels

6
Mutations continued...

• Classes 1-3 are most common and are associated
  with pancreatic insufficiency
• Classes 4-6 are rarer and typically patients do
  not have insufficiency
• most common worldwide is class 2 caused by
  deletion of phenylalanine at position 508
  (F508del) of CFTR
• its frequency varies between ethnic groups

7
Factors

• suggest that environmental factors, genes other
  than CFTR or both, modify the development,
  progression, and the diseases severity
• CFTR also regulates other apical membrane
  conductance pathways which are affected by
  mutations

8
Pulmonary infection

• CF leads to pathological changes in organs that
  express CFTR secretory cells, sinuses, lungs,
  pancreas, liver, and reproduction
• most striking changes seen in airways
• basic genetic defect causes chronic pulmonary
  infections

9
Conclusion

• Pulmonary infections are a result of genetic
  defect of CFTR
• many factors play into the severity of cystic
  fibrosis
• although there is no known cure for CF, with the
  increasing knowledge of the disease, the
  treatments become more effective, increasing life
  span of the CF patient

10
Questions