Genetic Disorders - Mendelian Disorders Flashcards
What are Mendelian Disorders?
Single gene alterations
4 types of Mendelian Disorders?
- Enzyme defects
- Membrane receptor and transport defects
- Alterations in structure/function/quantity of non-enzyme proteins
- Unusual reactions to drugs due to mutations
4 types of Mendelian Disorders?
- Enzyme defects
- Membrane receptor and transport defects
- Alterations in structure/function/quantity of non-enzyme proteins
- Unusual reactions to drugs due to mutations
3 consequences of Enzyme defects?
- Accumulation of substrate
- Lack of end product
- Failure to inactivate tissue-damaging substrate
What is an example of an enzyme defect that causes a toxic metabolite to accumulate?
Galactosemia - increased galactose is damaging
What is an example of an enzyme defect that causes failure to inactivate a tissue-damaging substrate?
Alpha1 - Antitrypsin deficiency
With an alpha1 - antitrypsin deficiency, what cannot be inactivated and causes tissue damage?
Can’t inactivate Elastase == Emphysema
What should you avoid doing if you have an alpha1 - antitrypsin deficiency?
Smoking
- Accelerates destruction of lung tissue
Homozygotes for what protein have 10% of normal functioning alpha1 - antitrypsin?
PiZZ protein
Those with PiZZ protein will eventually get?
Hepatocellular carcinoma and liver transplant
2 examples of membrane receptor and transport defects?
- Familial Hypercholesterolemia
2. Cystic Fibrosis
Describe what occurs with Familial Hypercholesterolemia?
- Decreased LDL receptor
- Defective transport of LDL into cells
- Secondary increased cholesterol
Cystic Fibrosis has what membrane receptor and transport defects?
Defective chloride ion transport
2 examples of alterations in structure and quantity of non-enzyme proteins?
Sickle cell disease
Thalassemias
Sickle cell disease has a defect in ____ of globin molecule
Structure
Thalassemias have a mutation in the globin gene that affects the ____ of globin chains synthesized
Amount
To what drug do those with G6PD deficiency have an adverse reaction?
Primaquine - Antimalarial drug
What is the result of those with G6PD deficiency when they take Primaquine?
Hemolytic Anemia
How is Marfan Syndrome inherited?
Autosomal Dominant
What gene and on what chromosome is usually mutated with Marfan Syndrome?
FBN1 on 15q21.1
What protein are defects present with Marfan Syndrome?
Fibrillin 1
2 results of Marfan syndrome?
- Loss of structural support in microfibril rich connective tissue
- Excessive activation of TGF-beta signaling
Loss of structural support in connective tissue and excessive activation of TGF-beta signaling is seen with what disease?
Marfan Syndrome
FBN1 on chromosome 15q21.1
Marfan Syndrome
Where are microfibrils commonly found?
Aorta, ligaments, ciliary zonules that support lens of eye
With Marfan syndrome, FBN1 has ____ mutations
1000
With Marfan syndrome, FBN2 mutations will cause?
Congenital Contractural Arachnodactyly
What normally controls the bioavailability of TGF-beta?
Fibrillin 1 – defective in Marfan Syndrome
Excessive activation of TGF-beta signaling can cause?
Inflammation, bad effects on vascular smooth muscle
Increased metalloproteases and bone overgrowth
Symptoms of Marfan Syndrome?
Tall, long extremities, double-jointed thumb, long head
Pectus Excavatum, aortic dissection
Ectopia lentis
Ectopia lentis
Dislocation of the lens of the eye
- Seen with Marfan syndrome
Tall, long extremities, double jointed thumb, ectopia lentis, aortic dissection?
Marfan Syndrome
Ehlers-Danlos Syndrome has a defect in synthesis/structure of?
Collagen
Classic Type1/2 Ehlers-Danlos gene mutations and inheritance pattern
COL5A1
COL5A2
- Autosomal Dominant
Symptoms of Classic Type 1/2 Ehlers-Danlos Syndrome?
Skin and joint hypermobility
Easy bruising and atrophic scars
Vascular Type 4 Ehlers-Danlos gene mutations and inheritance pattern
COL3A1
- Autosomal Dominant
Symptoms of Vascular Type 4 Ehlers-Danlos Syndrome?
Arterial or uterine rupture, thin skin and hyperextensibility
Kyphoscoliosis Type 6 Ehlers-Danlos mutations and inheritance pattern
PLOD1 - lysyl hydroxylase
- Autosomal Recessive
Symptoms of Kyphoscoliosis Type 6 Ehlers-Danlos Syndrome?
Congenital sclerosis
Hypotonia, joint laxity
Ocular fragility
Skin hard to repair and with gaping defects from minor injuries is seen with?
Ehler-Danlos Syndrome
2 mutation possibilities with Familial Hypercholesterolemia?
ApoB
PCSK9
Mutations with Familial Hypercholesterolemia directly cause?
Inadequate removal of LDL
Heterozygotes for Familial Hypercholesterolemia have a ____ fold increase in cholesterol and what symptoms?
2-3 fold
= Tendinous xanthomas
Homozygotes for Familial Hypercholesterolemia have a ____ fold increase in cholesterol and what symptoms?
5-6 fold
= Skin xanthomas, atherosclerosis and MI before age 20
MI before age 20 is suggestive of?
Homozygous Familial Hyperchoelsterolemia
ApoB or PCSK9
Familial Hypercholesterolemia
FBN1 on 15q21.1
Marfan Syndrome
FBN2 on 5q23.31
Marfan Syndrome - less common
