Chapter 12: The molecular, biochemical and cellular basis of genetic disease

Question 1

Substitution of 1178A>G in the ND4 subunit of complex I of the electron transport chain, account for majority of this mitochondrial disease

Answer 1

• Leber hereditary optic neuropathy (LHON)
• onset of blindness in young age
• optic nerve atrophy

Question 2

Point mutations in the ATPase subunit 6 gene lead to this mitochondrial disorder

Answer 2

• Leigh syndrome
• Early onset
• Progressive neurodegeneration
• hypotonia, developmental delay, optic strophy and respiratory abnormalities

Question 3

Point mutations in the tRNA^leu(UUR)

a mutation hot spot, most commonly 3243A>G

lead to this mitochondrial condition associated with encephalopathy, lactic acidosis and stroke like episodes

Answer 3

MELAS

Question 4

Point mutations in tRNA^lys most commonly 8344A>G

Answer 4

• MERRF
• Myoclonic epilepsy with ragged red fibres
• Myopathy
• ataxia
• sensorineural deafness
• demetia

Question 5

Homeoplasmic mutations in mtDNA

1555A>G mutation in the 12s rRNA gene

7445A>G mutation in the 12s rRNA gene

Answer 5

• Progressive sensorineural deafness
• induced by aminoglycoside antibiotics
• nonsyndromic sensorineural deafness

Question 6

mtDNA mutation

5kb large deletion

Answer 6

Kearns-Sayre Syndrome

• Progressive myopathy
• progressive external ophthalmoplegia of early onset
• cardiomyopathy
• heart block
• ptosis
• retinal pigmentation
• ataxia diabetes