7. Genetics Flashcards
Give examples of autosomal dominant disorders
- Aniridia
- Retinoblastoma
- Optic Atrophy
- Retinitis pigmentosa
- Marfan’s syndrome
Give examples of autosomal recessive disorders
- Stargardt’s disease
- Oculocutaneous albinism
- Some forms of retinitis pigmentosa
What are genes?
A hereditary unit consisting of a sequence of DNA
Describe DNA structure
1.Deoxyribose sugar
2.Nitrogenous base = Adenine bond to Thymine. Guanine bond to cytosine. Hydrogen bonds.
- Phosphate group. Bonds to other DNA with phosphodiester bond.
What is the role of DNA code? How is it linked to mutation?
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
What is gene regulation?
All cells contain the same genes but only some genes are used.
We need regulation to switch off unused genes.
What happens if there is no gene regulation?
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.
Why do optometrists need to be aware of the different genetic eye diseases?
To advice patient accordingly. Help to reduce life choice risk factors.
What is autosomal dominant?
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.
What is autosomal recessive?
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.
What is Aniridia? Signs and symptoms
Failure of iris to develop.
Failure of trabeculae to develop properly leading to secondary glaucoma.
Reduced VA
Photophobia.
Give example of a gene for development of the eye, and result of mutations of this gene.
PAX6
Mutation can cause Aniridia.
What can Mi gene mutations cause?
Microphthalmos- genetic failure of the eye to develop.
Compare the differences between degeneration and dystrophy of cornea.
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
Give examples of dystrophy
- Reiss Buckler dystrophy - pain due to recurrent erosions. (Bowman’s layer)
- Granular dystrophy - milky spots in stroma
- Lattice dystrophy - opaque lines in stroma
- Fuch’s endothelial dystrophy - wort like lumps called guttata on endothelial cells. Primarily in the center of cornea.
What is gene chromosome 21 linked to?
Congenital cataract
How is cataract classified?
By location. E.g. Anterior polar cataract
What is primary open angle glaucoma caused by?
By increased resistance to the outflow
What is secondary open angle glaucoma caused by?
By inflammation, haemorrhage or neovascularisation of the iris that impedes the outflow of aqueous humour.
What is congenital open angle glaucoma caused by?
By the obstruction to the aqueous drainage by developmental abnormalities.
Is cataracts autosomal dominant or recessive
Autosomal dominant
Is glaucoma autosomal dominant or recessive?
Dominant and recessive.
Juvenile onset type is autosomal dominant
Is retinitis pigmentosa autosomal dominant or recessive?
50% of cases in patients without any known affected family member
20% AD and 20% AR
Is retinoblastoma autosomal dominant or recessive?
Dominant.
Although 10% of patients who inherit the gene don’t develop retinoblastoma.
How do mutations cause retinitis pigmentosa?
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
What is the most common malignant ocular tumour to affect children?
Retinoblastoma. 1 in 17,000 in UK.
3% of childhood cancers.
What does the gene resulting in retinoblastoma code for and what does the mutation result in?
Codes for RB protein.
Mutation results in cell proliferation.( increased number of cells due to cell division)
What are the signs and symptoms of retinoblastoma?
Leukocoria - white pupil. White reflex not red.
Strabismus
Secondary glaucoma
Orbital inflammation
What causes optic atrophy?
Caused by damage to retinal ganglion cells resulting in cell death.
Is optic atrophy autosomal dominant or recessive?
Autosomal Dominant
Give signs and symptoms of optic atrophy
Slowly develop VA loss
Colour vision problems
Disc pallor (optic nerve axons are damaged, abnormal pale colour disc)
Is congenital nystagmus autosomal dominant or recessive?
Often dominant.
Although varied dependent on type
Is Marfan’s syndrome autosomal dominant or recessive?
Autosomal Dominant
What is Marfan’s syndrome?
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.
What is subluxation?
Dislocation of lens into vitreous
Is oculocutaneous albinism autosomal dominant or recessive?
Autosomal recessive
What is albinism caused by?
Failure to synthesise melanin from tyrosine due to enzyme deficiency
What are the signs and symptoms of albinism?
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
Is stargardt’s disease autosomal dominant or recessive?
Recessive.
Relatively common 1 in 8,000
Give example of vitreoretinal disorder
Stickler syndrome
Is stickler syndrome autosomal dominant or recessive?
Autosomal dominant
What are the signs of stickler syndrome?
Early high myopia
Lattice retinal degeneration
Cataracts
Glaucoma
Giant retinal tears (as in torn)
How is colour vision deficiency inherited?
Sex linked pattern of inheritance. Defective genes may be more frequently manifest in males. As females have two X chromosomes and Males have one.
