Genetic Disorders - Mendelian Disorders

Question 1

What are Mendelian Disorders?

Answer 1

Single gene alterations

Question 2

4 types of Mendelian Disorders?

Answer 2

1. Enzyme defects
2. Membrane receptor and transport defects
3. Alterations in structure/function/quantity of non-enzyme proteins
4. Unusual reactions to drugs due to mutations

Question 3

4 types of Mendelian Disorders?

Answer 3

1. Enzyme defects
2. Membrane receptor and transport defects
3. Alterations in structure/function/quantity of non-enzyme proteins
4. Unusual reactions to drugs due to mutations

Question 4

3 consequences of Enzyme defects?

Answer 4

1. Accumulation of substrate
2. Lack of end product
3. Failure to inactivate tissue-damaging substrate

Question 5

What is an example of an enzyme defect that causes a toxic metabolite to accumulate?

Answer 5

Galactosemia - increased galactose is damaging

Question 6

What is an example of an enzyme defect that causes failure to inactivate a tissue-damaging substrate?

Answer 6

Alpha1 - Antitrypsin deficiency

Question 7

With an alpha1 - antitrypsin deficiency, what cannot be inactivated and causes tissue damage?

Answer 7

Can’t inactivate Elastase == Emphysema

Question 8

What should you avoid doing if you have an alpha1 - antitrypsin deficiency?

Answer 8

Smoking

- Accelerates destruction of lung tissue

Question 9

Homozygotes for what protein have 10% of normal functioning alpha1 - antitrypsin?

Answer 9

PiZZ protein

Question 10

Those with PiZZ protein will eventually get?

Answer 10

Hepatocellular carcinoma and liver transplant

Question 11

2 examples of membrane receptor and transport defects?

Answer 11

1. Familial Hypercholesterolemia

2. Cystic Fibrosis

Question 12

Describe what occurs with Familial Hypercholesterolemia?

Answer 12

• Decreased LDL receptor
• Defective transport of LDL into cells
• Secondary increased cholesterol

Question 13

Cystic Fibrosis has what membrane receptor and transport defects?

Answer 13

Defective chloride ion transport

Question 14

2 examples of alterations in structure and quantity of non-enzyme proteins?

Answer 14

Sickle cell disease

Thalassemias

Question 15

Sickle cell disease has a defect in ____ of globin molecule

Answer 15

Structure

Question 16

Thalassemias have a mutation in the globin gene that affects the ____ of globin chains synthesized

Answer 16

Amount

Question 17

To what drug do those with G6PD deficiency have an adverse reaction?

Answer 17

Primaquine - Antimalarial drug

Question 18

What is the result of those with G6PD deficiency when they take Primaquine?

Answer 18

Hemolytic Anemia

Question 19

How is Marfan Syndrome inherited?

Answer 19

Autosomal Dominant

Question 20

What gene and on what chromosome is usually mutated with Marfan Syndrome?

Answer 20

FBN1 on 15q21.1

Question 21

What protein are defects present with Marfan Syndrome?

Answer 21

Fibrillin 1

Question 22

2 results of Marfan syndrome?

Answer 22

1. Loss of structural support in microfibril rich connective tissue
2. Excessive activation of TGF-beta signaling

Question 23

Loss of structural support in connective tissue and excessive activation of TGF-beta signaling is seen with what disease?

Answer 23

Marfan Syndrome

Question 24

FBN1 on chromosome 15q21.1

Answer 24

Marfan Syndrome

Question 25

Where are microfibrils commonly found?

Answer 25

Aorta, ligaments, ciliary zonules that support lens of eye

Question 26

With Marfan syndrome, FBN1 has ____ mutations

Answer 26

1000

Question 27

With Marfan syndrome, FBN2 mutations will cause?

Answer 27

Congenital Contractural Arachnodactyly

Question 28

What normally controls the bioavailability of TGF-beta?

Answer 28

Fibrillin 1 -- defective in Marfan Syndrome

Question 29

Excessive activation of TGF-beta signaling can cause?

Answer 29

Inflammation, bad effects on vascular smooth muscle | Increased metalloproteases and bone overgrowth

Question 30

Symptoms of Marfan Syndrome?

Answer 30

Tall, long extremities, double-jointed thumb, long head Pectus Excavatum, aortic dissection Ectopia lentis

Question 31

Ectopia lentis

Answer 31

Dislocation of the lens of the eye | - Seen with Marfan syndrome

Question 32

Tall, long extremities, double jointed thumb, ectopia lentis, aortic dissection?

Answer 32

Marfan Syndrome

Question 33

Ehlers-Danlos Syndrome has a defect in synthesis/structure of?

Answer 33

Collagen

Question 34

Classic Type1/2 Ehlers-Danlos gene mutations and inheritance pattern

Answer 34

COL5A1 COL5A2 - Autosomal Dominant

Question 35

Symptoms of Classic Type 1/2 Ehlers-Danlos Syndrome?

Answer 35

Skin and joint hypermobility | Easy bruising and atrophic scars

Question 36

Vascular Type 4 Ehlers-Danlos gene mutations and inheritance pattern

Answer 36

COL3A1 | - Autosomal Dominant

Question 37

Symptoms of Vascular Type 4 Ehlers-Danlos Syndrome?

Answer 37

Arterial or uterine rupture, thin skin and hyperextensibility

Question 38

Kyphoscoliosis Type 6 Ehlers-Danlos mutations and inheritance pattern

Answer 38

PLOD1 - lysyl hydroxylase | - Autosomal Recessive

Question 39

Symptoms of Kyphoscoliosis Type 6 Ehlers-Danlos Syndrome?

Answer 39

Congenital sclerosis Hypotonia, joint laxity Ocular fragility

Question 40

Skin hard to repair and with gaping defects from minor injuries is seen with?

Answer 40

Ehler-Danlos Syndrome

Question 41

2 mutation possibilities with Familial Hypercholesterolemia?

Answer 41

ApoB | PCSK9

Question 42

Mutations with Familial Hypercholesterolemia directly cause?

Answer 42

Inadequate removal of LDL

Question 43

Heterozygotes for Familial Hypercholesterolemia have a ____ fold increase in cholesterol and what symptoms?

Answer 43

2-3 fold | = Tendinous xanthomas

Question 44

Homozygotes for Familial Hypercholesterolemia have a ____ fold increase in cholesterol and what symptoms?

Answer 44

5-6 fold | = Skin xanthomas, atherosclerosis and MI before age 20

Question 45

MI before age 20 is suggestive of?

Answer 45

Homozygous Familial Hyperchoelsterolemia

Question 46

ApoB or PCSK9

Answer 46

Familial Hypercholesterolemia

Question 47

FBN1 on 15q21.1

Answer 47

Marfan Syndrome

Question 48

FBN2 on 5q23.31

Answer 48

Marfan Syndrome - less common