Genetic Diseases Flashcards
Which glands does CF affect?
Epithelial glands
Which receptor is deleted on chromosome 7 to cause CF?
CFTR
Which ion is transported through the CFTR channel?
Cl-
The deletion of the CFTR gene deletes the 2 nucleotide binding folds (NBFs) which do what in the cell?
bind ATP to provide energy for membrane transport
What happens to the mucous in CF?
becomes viscous cuz of low H2O moving into the mucous
What is the inheritance pattern of CF?
AR
Which race is at greatest risk for CF?
White people.
Which blood test can u do to screen babies for CF?
Immunoreactive trypsinogen (IRT)
True or False: IRT screening is an excellent test because it is 100% accurate in screening for CF.
False. There are false negatives.
What is the common respiratory problems in CF?
Frequent infections
What is the average lifespan of CF?
40 years
besides physical therapy and antibiotics, what drugs can u give to loosen secretions in CF?
Dornase
Which molecular biology tests can u run for the carrier detection in CF?
PCR amplification and gel elecrtophoresis
What aerosol prep can be done for gene therapy for CF?
Replacing the defective gene through recombinant vectors.
What is the function of the a1-antitrypsin enzyme in the cell?
it’s a serine protease inhibitor (serpin)
Which gene is a1-antitrypsin located on?
chromsome 14
Which 2 types of cells make a1-antitrypsin?
hepatocytes
macrophages
What is the major physiological fxn of a1-antitrypsin in the lung?
Protects it from elastase by using methionine 358 as bait
What other “activity” can cause oxidation of met358 can causing the same Sx as a1-antitrypsin?
Smoking
So what are the clinical manifestations of a1-antitrypsin deficiency?
Chronic severe pulmonary disease (emphysema) and liver disease
Which phenotypes are causitive for a1-antitrypsin deficiency?
ZZ (rare)
Pi(SZ) (~35%)
SS (~60%)
True or False: homozygous SS patients appear realtively normal.
True
In Pi(z), there is point mutation to change GAG (Lys) to what?
AAG (Glu)
In Pi(s), there is point mutation to change GAA (Val) to what?
GTA (Glu)
There is also a pitssburgh variant of a1-antitrypsin where there is a missense point mutation substituting Arg for what?
Met
Which gentotype (Piz, Pis, or Pittsburgh) leads to only ~15% of the a1-antitrypsin being secreted from the liver?
Pi(z)
Which gentotype (Piz, Pis, or Pittsburgh) leads to decreased stability of the a1-antitrypsin protein?
Pi(s)
Which gentotype (Piz, Pis, or Pittsburgh) leads to a lethal bleading disorder?
Pittsburgh variant
not surprised, steeler fans
Which genotype does most europeans have for a1-antitrypsin?
MM
At what age do you develop emphysema in ZZ genotype of a1-antitrypsin?
Middle age
True or False: a1-antitrypsin deficiencies are much more severe in smokers
True.
What is the genetic screening method for a1-antitrypsin deficiency?
ASO hybridization
What is the main therapy for a1-antitrypsin deficiency?
Injections of purified inhibitor
If the a1-antitrypsin is in the advanced stage, what is the main treatment?
Lung and liver transplantation
What are the common bugs to infect the airways in CF patients?
H. influenza, S. aureus, ***P. aeruginosa, Aspergillus, C. albicans
What is weird about the skin in CF patients?
It’s super salty
Which bug is a bad sign in CF patients?
Burkholderia cepacia
This is a dilation of bronchi due to irreversible destruction of bronchial walls.
Bronchiectasis
What is the main bug to cause chronic bronchiectasis?
P. aeruginosa
What is the main problem with the cilia to cause bronchiectasias?
Ciliary dyskinesia
This is an AR disorder of primary ciliary dyskinesia that has a triad of situs inversus, sinusitis, and bronciectasis.
Kartagener syndrome
Where is the mutation to cause Kartageners syndrome?
loss of the dynein arm
