Molecular,Biochem,Cellular Basis of Genetics 2

Question 1

What causes Acute Intermittent Porphyria?

Answer 1

Its caused by mutation in the gene encoding for porphobilinogen deaminase (PBGD)

Question 2

What kind of inheritance is Acute Intermittent Porphyria?

Answer 2

Autosomal Dominant

Question 3

What causes Acute Intermittent Porphyria to show symptoms?

Answer 3

When heme levels drop in hepatocytes

Question 4

How is Acute Intermittent Porphyria exacerbated?

Answer 4

Barbituates (Drugs)

Steroids

reducing diets

surgery

Question 5

What happens if exposed to precipitating factors?

Answer 5

increase of synthesis of P450, dropping heme levels and reducing the heme synthetic pathway also, via feedback inhibition of heme on δ-amino-levulinic acid (ALA) synthetase

Question 6

What is the clinical presentation of Acute Intermittent Porphyria?

Answer 6

acute episodes of a variety of gastrointestinal and neuropathic

symptoms; between episodes, the patient is healthy

Abdominal pain is the most common symptom (Vomiting)

Mental disturbance: (Confusion, Emotional upset, Hallucinations and psychosis)

Question 7

What is Familial Hypercholesterolemia?

Answer 7

is one of the type 2 familial hyperlipoproteinemias characterized by elevation of plasma cholesterol carried by LDL.

Question 8

What is the inheritance of Familialhypercholesterolemia?

Answer 8

Autosomal Dominant

Question 9

What is damaged in Familialhypercholesterolemia?

Answer 9

Mainly LDL receptors

4 possible proteins may cause Hypercholesterolemia or Hyperlipidemia

Question 10

What are the four proteins associated with Familialhypercholesterolemia?

Answer 10

1. LDL receptor mutation: Chromosome 19
2. Mutations in the LDL receptor binding domain of ApoB-100: Chromosome 2
   
   • impairs LDL binding to its receptor by ApoB-100
3. PCSK9 protease activity leads to degradation of the LDL receptor: Ch 1
4. Mutation in ARH adaptor protein,
   
   • links the receptor to the endocytic machinery of the coated pit causing clustering of the LDL receptor-ApoB-100 complex in clathrin-coated pits: Ch 1

Question 11

What is the most important gene abnormality in FamilialHypercholesterolemia? Why?

Answer 11

PCSK9 protease gene

Mutation of this gene will cause the disease but some variants lower the plasma LDL cholesterol level giving some protection from coronary hearts disease

Question 12

What are some symptoms of Familial Hypercholesterolemia?

Answer 12

premature heart disease

xanthomas (homozygous for the gene)

arcus corneae (fat deposits in cornea)

Question 13

What is deficient in Cystic Fibrosis?

Answer 13

pancreatic enzymes

Question 14

How do you restore normal digestion in Cystic Fibrosis?

Answer 14

pancreatic enzyme supplement

Question 15

What is wrong with Cystic Fibrosis males?

Answer 15

They lack a vas deferens and therefore are infertile

Question 16

How is the stool of CF patients?

Answer 16

Greasy, lighter in color,

Question 17

What is the major cause of Cystic Fibrosis?

Answer 17

Psudomonas aeruginosa

Question 18

What are the 2 muscular dystrophies resulting from defects in dystrophin gene?

Answer 18

1. Duchenne
2. Beckers

Question 19

What type of inheritance is Duchenne and Beckers?

Answer 19

X-Linked

Question 20

What are the clinical features of Duchenne muscular dystrophy?

Answer 20

1. gower maneuvers
2. High lvs of creatinine kinase (CK)
3. boys are normal first year of life
4. slow developing progression of muscle weakness
5. gait
6. lumbar lordosis
7. Wheelchair bound by age 12
8. joint contracture
9. pseudohyperthrophy: increase in the size of calf (calf muscles replaced by fat and fibrous connective tissue)

Question 21

Greatly elevated Creatinine levels may indicate what disease?

Answer 21

Duchenne Muscle Dystrophy

Question 22

What are the clinical features of Becker’s Muscle Dystrophy?

Answer 22

sames as Duchennes but at a slower onset

Question 23

Genetically, Duchenne and Becker’s exemplify what?

Answer 23

Allelic Heterogeneity (different mutation same gene)

Question 24

Deletions in the codon for Duchenne MD is due to what?

Answer 24

a frameshift mutation

Question 25

Deletions in the codon for Becker’s MD is caused by?

Answer 25

In-frame mutation

Question 26

What is the frequency for DMD and Becker’s?

Answer 26

60%

Question 27

What is Ehrler-Danlos Syndrome?

Answer 27

genetic defect in collagen structure, synthesis, secretion,

or degradation.

Question 28

What is the clinical presentation of Ehrler-Danlos?

Answer 28

Hypermobility

Hyperelasticity

Skin fragility

Tendency to bleed

Aortic Aneurysm

Cigarette Paper skin

Question 29

What do Type 1 and Typer 2 Ehrler-Danlos have in common?

Answer 29

The mutations are linked to loci that contain the COL5A1 gene or COL5A2 genes; encoding the alpha chains of type V collagen, leading to defective type V collagen

Question 30

What is the frequency of Type 1 and 2 Ehrler-Danlos Syndrome?

Answer 30

1/30,000

Question 31

What is the frequency of Type 3 Ehrler-Danlos Syndrome and how does it presents?

Answer 31

1/5,000

Patient may have arterial or uterine rupture

Question 32

What type of collagen is associated with type 4 EDS and where would you find it?

Answer 32

Reticular Type 3 Collagen

Found in vasculature and skin

Question 33

What is the deficiency found in type 6 EDS?

Answer 33

Lysyl Hydroxylase

Question 34

Whats wrong in Type 7 EDS?

Answer 34

Can’t turn procollagen to collagen

Question 35

With what can we associate type 8 EDS?

Answer 35

Dermatosporaxsis

skin fragility

Question 36

Of the two dystrophies resulting from a mutation in the dystrophin gene, which is more severe?

Answer 36

Duchenne: more severe/lack of dystrophin

Beckers: less severe

Question 37

What is the defect gene in Ehrler-Danlos Syndrome?

Answer 37

Col3A1

Question 38

What is the major risk with type 3 Ehrler-Danlos Syndrome?

Answer 38

Death