Physiology

• What was the old saying about babies that tasted salty when kissed?

  They are bewitched and shall soon die
• Cystic fibrosis can be described as a respiratory what?

  Channelopathy
• What type of genetic disorder is cystic fibrosis?

  Autosomal recessive
• Cystic fibrosis primarily affects which type of tissue and what process?

  Epithelial tissue & electrolyte transport
• What is the approximate incidence of CF in the UK births?

  1 in 2,500
• What is the approximate carrier frequency of CF in the UK?

  1 in 20
• What was the typical survival rate for CF patients 50 years ago?

  Survival past 1 year was rare
• Which high-income country is mentioned in relation to cystic fibrosis?

  USA
• Blockage of small bile ducts and problems with liver function occur in what percentage of CF patients?

  5%
• Blockage of the pancreatic ducts, preventing secretion of digestive enzymes, occurs in what percentage of CF patients?

  65%
• Small intestine obstructions due to thick content occur in what percentage of CF newborns?

  10%
• What is the term for small intestine obstructions in CF newborns?

  Meconium ilius
• What percentage of males with CF experience absence of the vas deferens, leading to infertility?

  95%
• What happens in the skin of patients with CF?

  Excess excretion of NaCl via sweat
• If both parents are carriers of an autosomal recessive gene, what is the chance of them passing on the mutated gene?

  50%
• What happens in the airways of patients with CF?

  Clogging & infection
• In autosomal recessive inheritance, what is the chance of a child being a carrier if both parents are carriers?

  100%
• In autosomal recessive inheritance, what is the chance of a child inheriting CF if only one parent is a carrier?

  0%
• What is the full name of the CFTR protein?

  Cystic fibrosis transmembrane conductance regulator
• The CFTR protein functions as what type of channel?

  $Cl^-$ channel
• The CFTR channel is activated by what molecule?

  cAMP
• Approximately how many mutations are assumed to cause CF?

  ~2100 mutations
• What contributes to variable penetrance in CF?

  Environmental and genetic factors
• What does "1 protein = 1 functional channel" mean in the context of CFTR?

  Each CFTR protein forms one channel
• What are the CFTR mutation classes related to impaired production?

  • (I) Impaired production – stop codons, nonsense mediated decay, e.g. G542X, W1282X
  • (VII) Impaired production – no full length mRNA, deleted sequences
• Which mutation class involves impaired trafficking of CFTR?

  (II)
• Which mutation class involves impaired gating of CFTR?

  (III)
• Which mutation class involves decreased conductance of CFTR?

  (IV)
• Which mutation class involves decreased membrane stability?

  (VI)
• Which mutation class involves decreased protein production via abnormal splicing?


  (V)
• What is the allelic frequency of the $ΔF508$ mutation?


  Up to 90%
• What is the approximate allelic frequency of the G551D mutation?

  ~1-3%
• What determines the severity of CF?

  Mutation
• Which mutation classes generally lead to more severe CF?

  Class I to III, VII
• Which mutation classes generally lead to milder CF?

  Class IV, V, VI
• What characterizes the lung pathology in CF?

  Viscous airway mucous
• What is the result of some mild mutations sitting just under the clinical threshold?

  Carrier / Non CF
• What is a common cause of death in CF patients?

  Tissue degeneration
• What does ENaC stand for?

  Epithelial Sodium Channel
• What does the diagram with $Cl^-$, $Na^+$, $K^+$, ENaC, CFTR, and $H_2O$ represent?


  Upper airway $Na^+$ and $Cl^-$ handling