1-30 Mitochondrial Disorders and Inheritance

Question 1

Mitochondrial choromosme

Answer 1

double stranded closed circle, all exact same length
22 tRNAs for translation
13 polypeptides
small and large rRNAs

no genes that can enable DNA repair
information on both strands

uniquely organized: no intervening sequences (all exons/continuous sequence) no 5’ or 3’ non-coding regions

unique genetic code (differs from nuclear code)

all mtDNA come from the mother: maternal/mitochondrial inheritance, because each cell contians 100-1000s of mito and each mitto contains 2-10 copies of mtDNA the inheritance in mosaic: heteroplasmy

Question 2

Common signs of mitochondrial disease

Answer 2

Eyes:
ptosis (droopy eyelids)
external ophthalmoplegia (impaired ability to move eyes)
pigmentary retinopathy (retinal degeneration)

Muscle:
myopathy: muscle fibers don’t function
weakness, exercise intolerance

heart: cardiomyopathy

diabetes mellitus

CNS: seizures, dementia, migraine, ataxia, spasticity, stroke-like episodes

**Variable phenotype within individuals, heterogenous, age of onset varies

Question 3

MELAS

MERRF

NARP

Answer 3

point mutations

Mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes: onset childhood, seizures, recurrent headaches, vomiting, myopathy, development usually normal, affects the tRNA leucine from the mitochondrial genome

myoclonic epilepsy with ragged red fibers

neuropathy, ataxia, retinitis pigmentosa

Question 4

Kearns-Sayre syndrom (KSS)- ophthalmoplegia Plus

Answer 4

mtDNA deletions: commonality in patients in difficulty moving eyes and other manifestations based on amount of genome deleted

Question 5

Alpers-Huttenlocher syndrome

Answer 5

mito depletion syndromes caused by mutation in polymerase gamma which is needed for mtDNA replication

characterized by intractable seizures, progressive loss of brain function, liver failure, childhood onset

Question 6

mitochondrial deletion syndromes

Answer 6

autosomal recessive disorders characterized by depletion of mtDNA, affects brain muscle and liver

Question 7

heteroplasmy

Answer 7

mosaicism: when mutation in mtDNA, mitochondria within a single cell will have mtDNAs with diff sequences (some with mutation some without)

could be that a certain threshold of mutant mitochondria needed for any effect to be detected, each cell division can be different, variable expression of disease

high mutation rate (5-10 times the mutation rate for nuclear DNA)