Sex Linked and Mitochondral Disorders

Question 1

What is the mean onset of BMD?

Answer 1

11 years.

Question 2

How can the reading frame in DMD be corrected?

Answer 2

By using exon skipping.

Question 3

How can the effect of muscular dystrophy be measured?

Answer 3

By measuring serum creatine kinase (reduces with muscular dystrophy).

Question 4

What is X inactivation?

Why is it needed?

How does it happen?

Answer 4

• Since males and females need the same dosage of X-specific gene products, females must deactivate one X chromosome to compensate.
• Inactivation spreads from an X inactivation centre on the chromosome.
• The XIST gene maintains the inactivated state of the chromosome.

Question 5

What is a Barr body?

Answer 5

An inactive X chromatin.

Question 6

How do X linked dominant inheritance patterns differ from that of autosomal inheritance patterns?

Answer 6

1 - Excess of affected females.

2 - No male to male or male to female transmission.

Question 7

List 3 X linked diseases.

Are they dominant or recessive?

Answer 7

Recessive:

1 - DMD.

2 - BMD.

3 - Congenital adrenal hyperplasia.

Dominant:

1 - Vitamin D resistant rickets.

Question 8

Give an example of sex limitation.

Answer 8

Virilisation of female infants with congenital adrenal hyperplasia.

Question 9

How many genes are contained within the mitochondrial genome?

Answer 9

37.

Question 10

What is the collective function of the proteins produced by the genes of the mitochondrial genome?

Answer 10

They are components of the respiratory chain.

• Most mitochondrial proteins are produced from nuclear genes.

Question 11

Why is mitochondrial inheritance exclusively maternal?

Answer 11

Because sperm mitochondria are actively expelled from the fertilised egg.

Question 12

Why is mitochondrial inheritance said to show heteroplasmy?

Answer 12

Because if a mutation arises in mitochondrial DNA, it will create a mixed population of normal and mutated mitochondria within the cell.

Question 13

What happens to the mitochondria of a cell upon mitosis?

Answer 13

They are split and randomly distribute among daughter cells.

Question 14

List 7 characteristic features of mitochondrial disorders.

Answer 14

1 - Muscle weakness.

2 - Epilepsy.

3 - Deafness.

4 - Optic atrophy.

5 - Diabetes.

6 - Cardiomyopathy.

7 - Aplastic anaemia.

Question 15

List 2 mitochondrial DNA disorders.

Answer 15

1 - Kearns-Sayre syndrome.

2 - MELAS.

Question 16

What is the main sign of Kearns-Sayre syndrome?

Answer 16

Chronic progressive external opthalmoplegia (paralysis of the eye muscles).

Question 17

What does MELAS stand for?

Answer 17

Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes.

Question 18

What is the significance of nuclear genes encoding most mitochondrial proteins?

Answer 18

Disorders of mitochondria don’t always result from mutations in mitochondrial DNA.

Question 19

What is the threshold effect?

Answer 19

Phenotypic manifestation of the genetic defect occurs only when a threshold level is exceeded.

Question 20

Why might an affected mother with a mitochondrial disorder produce offspring that do not express the phenotype (are carriers)?

Answer 20

• Due to the threshold effect.

- Heteroplasmy means the fertilised egg did not contain enough mitochondria to allow the phenotype to manifest.