7. Genetics

Question 1

Give examples of autosomal dominant disorders

Answer 1

1. Aniridia
2. Retinoblastoma
3. Optic Atrophy
4. Retinitis pigmentosa
5. Marfan’s syndrome

Question 2

Give examples of autosomal recessive disorders

Answer 2

1. Stargardt’s disease
2. Oculocutaneous albinism
3. Some forms of retinitis pigmentosa

Question 3

What are genes?

Answer 3

A hereditary unit consisting of a sequence of DNA

Question 4

Describe DNA structure

Answer 4

1.Deoxyribose sugar

2.Nitrogenous base = Adenine bond to Thymine. Guanine bond to cytosine. Hydrogen bonds.

3. Phosphate group. Bonds to other DNA with phosphodiester bond.

Question 5

What is the role of DNA code? How is it linked to mutation?

Answer 5

Tells a cell how to build a protein.
Influences the structure and function of cells
Gene mutations can occur causing altered protein
Mutations can be substitutions

Question 6

What is gene regulation?

Answer 6

All cells contain the same genes but only some genes are used.
We need regulation to switch off unused genes.

Question 7

What happens if there is no gene regulation?

Answer 7

This is linked to cancer as some genes control rate of cell division.
So if these genes are switched off, cell division can’t be controlled leading to oncogenesis.

Question 8

Why do optometrists need to be aware of the different genetic eye diseases?

Answer 8

To advice patient accordingly. Help to reduce life choice risk factors.

Question 9

What is autosomal dominant?

Answer 9

Only one mutated copy of the gene will be necessary for a person to be affected.
50% chance that a child will inherit the mutated gene.
Only need one affected parent.

Question 10

What is autosomal recessive?

Answer 10

Two copies of the mutated gene will be necessary for a person to be affected. 25% chance that a child will inherit the mutated gene.
Unaffected parent who both carry a single copy of the mutated gene.

Question 11

What is Aniridia? Signs and symptoms

Answer 11

Failure of iris to develop.
Failure of trabeculae to develop properly leading to secondary glaucoma.
Reduced VA
Photophobia.

Question 12

Give example of a gene for development of the eye, and result of mutations of this gene.

Answer 12

PAX6
Mutation can cause Aniridia.

Question 13

What can Mi gene mutations cause?

Answer 13

Microphthalmos- genetic failure of the eye to develop.

Question 14

Compare the differences between degeneration and dystrophy of cornea.

Answer 14

Degeneration:
Tissue changes
Result of disease or aging
Rare to have genetic predisposition
Associated with systemic diseases (disease affecting the whole body)
Changes caused by inflammation

Dystrophy:
Autosomal dominant inheritance
Onset at 20, stable at 40
No association with systemic or ocular disease
Bilateral
Vary in severity
Central location
Involve a single layer of cornea

Question 15

Give examples of dystrophy

Answer 15

1. Reiss Buckler dystrophy - pain due to recurrent erosions. (Bowman’s layer)
2. Granular dystrophy - milky spots in stroma
3. Lattice dystrophy - opaque lines in stroma
4. Fuch’s endothelial dystrophy - wort like lumps called guttata on endothelial cells. Primarily in the center of cornea.

Question 16

What is gene chromosome 21 linked to?

Answer 16

Congenital cataract

Question 17

How is cataract classified?

Answer 17

By location. E.g. Anterior polar cataract

Question 18

What is primary open angle glaucoma caused by?

Answer 18

By increased resistance to the outflow

Question 19

What is secondary open angle glaucoma caused by?

Answer 19

By inflammation, haemorrhage or neovascularisation of the iris that impedes the outflow of aqueous humour.

Question 20

What is congenital open angle glaucoma caused by?

Answer 20

By the obstruction to the aqueous drainage by developmental abnormalities.

Question 21

Is cataracts autosomal dominant or recessive

Answer 21

Autosomal dominant

Question 22

Is glaucoma autosomal dominant or recessive?

Answer 22

Dominant and recessive.
Juvenile onset type is autosomal dominant

Question 23

Is retinitis pigmentosa autosomal dominant or recessive?

Answer 23

50% of cases in patients without any known affected family member
20% AD and 20% AR

Question 24

Is retinoblastoma autosomal dominant or recessive?

Answer 24

Dominant.
Although 10% of patients who inherit the gene don’t develop retinoblastoma.

Question 25

How do mutations cause retinitis pigmentosa?

Answer 25

Mutations result in abnormal rhodopsin which causes photoreceptor death, specifically rods.

First symptom is nyctalopia (night blindness)

Other symptoms:
Visual field loss spreads to periphery then to center
Bone spicule pigmentation
Degeneration of ganglion cells

Question 26

What is the most common malignant ocular tumour to affect children?

Answer 26

Retinoblastoma. 1 in 17,000 in UK.
3% of childhood cancers.

Question 27

What does the gene resulting in retinoblastoma code for and what does the mutation result in?

Answer 27

Codes for RB protein.
Mutation results in cell proliferation.( increased number of cells due to cell division)

Question 28

What are the signs and symptoms of retinoblastoma?

Answer 28

Leukocoria - white pupil. White reflex not red.
Strabismus
Secondary glaucoma
Orbital inflammation

Question 29

What causes optic atrophy?

Answer 29

Caused by damage to retinal ganglion cells resulting in cell death.

Question 30

Is optic atrophy autosomal dominant or recessive?

Answer 30

Autosomal Dominant

Question 31

Give signs and symptoms of optic atrophy

Answer 31

Slowly develop VA loss
Colour vision problems
Disc pallor (optic nerve axons are damaged, abnormal pale colour disc)

Question 32

Is congenital nystagmus autosomal dominant or recessive?

Answer 32

Often dominant.
Although varied dependent on type

Question 33

Is Marfan’s syndrome autosomal dominant or recessive?

Answer 33

Autosomal Dominant

Question 34

What is Marfan’s syndrome?

Answer 34

Affects the elastic fibres of connective tissue. This syndrome affects:
The skeleton - tend to have longer arms and legs
The eye - suspensory ligaments is affected. Subluxation - dislocation of lens into vitreous
The heart - disorganisation of collagen can lead to thrombosis and collapse heart valves.

Question 35

What is subluxation?

Answer 35

Dislocation of lens into vitreous

Question 36

Is oculocutaneous albinism autosomal dominant or recessive?

Answer 36

Autosomal recessive

Question 37

What is albinism caused by?

Answer 37

Failure to synthesise melanin from tyrosine due to enzyme deficiency

Question 38

What are the signs and symptoms of albinism?

Answer 38

Pigment of skin and hair may be lighter
Fundus usually pale
Reduced vision
Pendular nystagmus
Iris transillumination
Foveal hypoplasia (foveal pit doesn’t develop properly)
Strabismus

Question 39

Is stargardt’s disease autosomal dominant or recessive?

Answer 39

Recessive.
Relatively common 1 in 8,000

Question 40

Give example of vitreoretinal disorder

Answer 40

Stickler syndrome

Question 41

Is stickler syndrome autosomal dominant or recessive?

Answer 41

Autosomal dominant

Question 42

What are the signs of stickler syndrome?

Answer 42

Early high myopia
Lattice retinal degeneration
Cataracts
Glaucoma
Giant retinal tears (as in torn)

Question 43

How is colour vision deficiency inherited?

Answer 43

Sex linked pattern of inheritance. Defective genes may be more frequently manifest in males. As females have two X chromosomes and Males have one.