Cystic Fibrosis Flashcards
Define monogenic
strong genetic influence by 1 gene.
define autosomal
gene on one of the 22 autosomes there is 2 copies of each per cell/
define recessive
need two defective copies to be affected by the disease.
define carriers
heterozygotes who aren’t affected
define dominant
inherited just one copy of the mutated gene, from either parent, is sufficient for the person to be affected.
define congenital
inherited (present from birth)
how is Cystic Fibrosis (CF) defined by these terms
(congenital) fatal monogenic recessive disorder.
what is CF caused by
mutations in the gene for the CF transmembrane regulator gene “CFTR” gene. It is a Cl- channel.
what population is CF most common in
caucasians.
what is the inheritance pattern for CF
autosomal recessive.
referring to the phenotype of CF what are the “classic triad of clinical manifestations”
- Increased sweat Na and Cl
- pancreatic insufficiency
- Pulmonary infection
the pathophysiology of CF is due to
the production of thick mucus
male infertility caused by CF is due to
congenital bilateral absence of the Vas deferens
Those with CF are at risk of recurrent infections with
Pseudomonas aeruginosa.
those with CF are at risk of developing which metabolic disorder
diabetes mellitus.
Detail the classic investigation of CF
There a range of causative mutations for CF so DNA testing in not the frontline of testing.
Investigation of clinical and family history
Newborn screening: Measure the IRT (immunoreactive trypsinogen), it is increase in CF.
Genotype: for more common mutations,
2 mutations =CF
1 mutation= sweat test
no mutation= not CF
Sweat test: tests electrolytes in the sweat. CF patietns secrete a normal volume of sweat but they cannot reabsorbed NaCl from the sweat resulting in increased levels.
Describe the interpretation of a sweat test.
Sweat Cl- (in mmol/L)
60: CF
30-59: borderline
29: normal
Describe CFs impact on the Lungs.
Cl and Na transport across the epithelia is affected
Theres a decrease in the Cl- channel activity
this leads to a change in ENaC (epithelial Na Channel)
this leads to an increase in Na (and h2o) absorption.
This leads to a decreased water content in secretions, this causes mucus to become thicker and further causes impaired flow, plugs and obstructions.
This leads to a decrease in pericillary volume, the thick mucus leads to poor cilary clearance of pathogens and results in recurrent infections.
Describe the impact fo CF on the GIT.
Cl and Na transport across the epithelia is affected
Theres a decrease in the Cl- channel activity
this leads to a change in ENaC (epithelial Na Channel)
this leads to an increase in Na (and h2o) absorption.
This leads to a decreased water content in secretions, this causes mucus to become thicker and further causes impaired flow, plugs and obstructions.
The blockage of pancreatic ducts leads to aloss of water from the GIT, this leads to constipation, renal prolapse ad meconium ileus (blockage of the intestine)
Describe the impact of CF on sweat glands
these is a decrease in Cl- channel activity
there is a change to the regulation of ENaC this leads to a DECREASE in Na absorption (vs an increase in the airways and GIT). this results in an increased sweat NaCl concentration.
What are some possible heterozygote advantages to CF
CF mutations could be protective against diarrhoea
Resistance to typhoid fever.
where is the CFTR gene located
Chromosome 7 (7q31-q32)
What is the most common mutation associated with CF
delta F508 (others include: G542X, G55ID, 621 + 1 G>T)
what do mutations in the CFTR gene result in
alternative splicing produces alternative (non functional) proteins.
What are the types of mutations that could cause CF
missense, nonsense (truncation), deletion, insertion and frameshift (due to insertion or deletion)
describe the classic phenotype of CF
complete loss of CFTR function as a Cl channel, this results in:
- Pancreatic insufficiency
- COPD
- Abnormal sweat electrolyte concentrations
- Absence of vas deferens in males
CF can be mono-organ, what does this mean.
Mono-symptomatic/mono-organ forms of CF effect only one organ, the most effected is the pancreas the least is the lungs.
