Cystic Fibrosis Flashcards
where is CF most common?
it is the most common autosomal recessive disorder in Caucasians (1/2500)
what is trait of CF that was treated as a death sentence in history?
salty skin
who named CF of the pancreas? What else is it called?
Dorothy Anderson (1938). Mucoviscidosis
What gene codes for CF? When was it discovered?
the CFTR gene, in 1989
the first study of CF was done where ad when? What was the result of this study?(linkage study)
in Danish families as they had large families, in 1985. They thought that the PON gene was the cause of CF
a second linkage study on CF was performed when?
in Amish people/ Hutterite Family, 1986
what were the results of this second linkage analysis study?
that the CF gene is not due to PON gene.
the CF gene should be close to the PON gene. The CF gene is on chromosome 7. CF is a highly homogenous disease
what are the symptoms of the CF disease? (mutation in CFTR)
it is a multisystem disorder, affecting the pulmonary, pancreatic, GI, reproductive organ systems.
CFTR gene codes for?
a membrane chloride channel in the apical membrane of secretory epithelia producing: mucus, sweat, saliva, tears, digestive enzyme.
the passage of chloride ions help what?
the movement of water in tissues
what is the normal and pathological process of the airways?
normally: CFTR makes Cl- go out of cell, it inhibits epithelial sodium channel (ENaC) so that less sodium enters the cell. Therefore osmotic eq. is maintained.
PATHOLOGY: CFTR doesn’t allow CL- ion secretion correctly, and cannot inhibit ENaC either. The CF mucus secretions are hyper viscous
hyper viscosity affects?
the pancreas by blocking the pancreatic ducts
what kind of disease is CF
is a highly allelic heterogeneous disease
what are the 5 classifications of mutations?
~ no synthesis of protein ~ block in processing of the protein ~ block in channel regulation ~ altered conductance ~ reduced synthesis
the most common mutation of CFTR gene is
F508 -66%
explain the multi-step screening
~ Diagnosis on clinical grounds: with symptoms of meconium ileus, delayed passage of meconium, salty tasting skin
~Chloride sweat test
~genetic screening at 3 levels
explain why the concentration of chloride increases in sweat of CF
a sweat gland has 2 parts : a secretory part an a re-adsorptive part which reabsorbes NaCl thus the gland secretes hypotonic sweat, however in CF patients there is no reabsorption of NaCl.
~ >60mEq/L
CFTR acts as an ‘in’ and ‘out’ for Cl in what locations
- ‘in’ sweat glands
- ‘out’ airways
what are the 3 levels for genetic screening
~1: all common mutations, reverse dot blot
~2: screening of coding sequences
~3: search for rearrangement (deletions/duplications)
what are hemoglobinopathies
the most common mendelian disorders, are inherited disorders characterized by mutation affecting one of the globin chains of Hb
Hb differ based on
~the moment in which they are expressed
~the degree of affinity with O2
~physico-chemical properties
affinity for O2 of Hb depends
~temperature
~concentration of 2,3-diphosphoglycerate
~pH of blood (Bohr effect)
how many copies of the CFTR gene does the alpha subunit contain
one alpha contains 2
quantitative defects of hemoglobinopathies are?
thalassemias alpha and beta, are classified according to the presence of the disease causing mutation in the alpha beta genes
sickle cell disease is inherited as a
autosomal recessive trait, caused by a SNS in the beta globin gene of chr11
what happens to mutated RBS when exposed to O2
they polymerise under low O2 conditions and form bundles
malaria is caused by
plasmodium falciparum
