Chapter 5: Molecular Genetics

Question 1

What percentage of childhood blindness is due to a genetic cause?

Answer 1

Approximately 50%

Question 2

What percentage of exons code for transcription factors?

Answer 2

10%

Question 3

What do PAX2 mutations cause?

Answer 3

Optic nerve colobomas and renal hypoplasia

Question 4

What do PAX3 mutations cause?

Answer 4

Waardenberg syndrome with dystopia canthorum (types WS1 and WS3)

Question 5

What do PAX6 mutations cause?

Answer 5

They cause almost all cases of aniridia, occasional cases of Peters Anomaly, as well as other rarer phenotypes (i.e. AD Keratitis, Dominant Foveal Hypoplasia, etc)

Question 6

What disease do patients with xeroderma pigmentosa have a higher risk of developing? Why?

Answer 6

Ocular squamous cell carcinoma, because of loss of DNA-repair enzyme functionality

Question 7

What are the sub-divisions of mitochondrial mutations that cause disease?

Answer 7

• large rearrangements of mtDNA
• mutations of mtDNA encoded rRNA
• mutations of mtDNA encoded tRNA
• missense and nonsense mutations

Question 8

What is CPEO? What does it stand for? What is its cause?

Answer 8

Chronic Progressive External Ophthalmoplegia, involves progressive ptosis and paralysis of eye muscles associated with ragged red myopathy

due to a deletion of mitochondrial DNA

Question 9

What infraorbital disorder do CPEO patients commonly have?

Answer 9

retinitis pigmentosa, although it usually doesn’t create a significant visual disturbance

Question 10

What is Kearns-Sayre Syndrome?

Answer 10

A more severe form of CPEO, also associated with heart block and severe retinitis pigmentosa with marked visual disturbance

due to deletion of mtDNA

Question 11

What is Leber Hereditary Optic Neuropathy? What causes it? Who is typically affected?

Answer 11

optic atrophy +/- peripapillary microangiopathy

Due to a mutation of NADH hydrogenase in mitochondria

Men more commonly affected than women

Variable prognosis depending on site of mutation

Question 12

What is Neuropathy, Ataxia, and Retinitis Pigmentosa? What causes it? What disease is it related to?

Answer 12

Same symptoms as in the name, caused by a single base pair mutation at nucleotide position 8993 of ATP-ase gene 6

phenotype occurs when 80% effected–> Leigh Syndrome

Question 13

What genetic defect is associated with both MELAS and MIDD?

Answer 13

They are both associated with an A–>G mutation @ position 3243 of mtDNA (affects mt tRNA)

Question 14

What genetic mutation is associated with exfoliation syndrome?

Answer 14

a LOXL1 mutation (associated, not the cause)