Mitochondrial Genetics and Disease

Question 1

What is the function of the mitochondria?

Answer 1

provide cellular energy in the form of ATP for the cell

Question 2

What are the two ways the mitochondria can provide energy?

Answer 2

Electron transport chain and oxidative phosphorylation

Question 3

Mitochondria have their own _____

Answer 3

DNA

Question 4

What are the characteristics of mitochondrial disorders?

Answer 4

clinical variability and age related progression of disease

Question 5

What does MERRF stand for?

Answer 5

myoclonus epilepsy with ragged red fibers

Question 6

What does MELAS stand for?

Answer 6

mitochondrial encephalopathy lactic acidosis and stroke like episodes

Question 7

What does KSS stand for?

Answer 7

Kearns-sayre syndrome

Question 8

What does CPEO stand for?

Answer 8

chronic progressive external ophthalmoplegia

Question 9

What does LHON stand for?

Answer 9

leber hereditary optic neuropathy

Question 10

What is a mitochondrial myopathy?

Answer 10

muscle disease caused by mitochondrial disfunction

Question 11

What are clinical characteristics of mitochondrial myopathies?

Answer 11

muscle weakness
exercise intolerance
lactic acidosis
neurological signs: mitochondrial encephalopathies
other abnormalities: vomiting, seizures, dementia, stroke like episodes, ptosis, ophthalmoplegia, blindness, cardiomyopathy

Question 12

What are ragged red fibers?

Answer 12

aggregates of abnormal mitochondria that form red sarcolemmal blotches

Question 13

Are mitochondria maternally or paternally inherited?

Answer 13

maternally

Question 14

What is heteroplasmy?

Answer 14

when a mtDNA mutation occurs, a mixture of normal mitochondria and mutant mitochondria occurs in one cell

Question 15

What is threshold in mitochondrial disease?

Answer 15

when there is too many mutant mitochondria, disease will result

Question 16

In the ETC, enzyme complexes I to IV oxidize what?

Answer 16

NADH and FADH2

Question 17

What is complex V?

Answer 17

ATP synthase

Question 18

Complexes I through V are encoded by what?

Answer 18

nuclear and mitochondrial DNA

Question 19

Does mtDNA have a repair mechanism?

Answer 19

no

Question 20

______ mutations in mtDNA tRNA goes lead to MELAS and MERRF

Answer 20

point

Question 21

mtDNA ______ deletions and rearrangements lead to KSS and CPEO

Answer 21

genome

Question 22

What are the clinical features of MERRF?

Answer 22

myoclonus (involuntary jerking of the muscle)
myoclonic epilepsy
ataxia
ragged red fibers
seizures

Question 23

90% of MERRF caused by what?

Answer 23

2 mutations of tRNA Lys

Question 24

85% of MERFF cases due to ___ to ___ mutation in mtDNA tRNA lys one
5% are due to ____ to ____

Answer 24

A to G; G to C

Question 25

What are characteristics of MELAS?

Answer 25

``` seizures blindness headaches anorexia recurrent vomiting lactic acidosis ragged red fibers ```

Question 26

When is the age of onset for MELAS?

Answer 26

2-10 years

Question 27

What is the typical cause of MELAS?

Answer 27

A3243B mutation in tRNA leu

Question 28

What are the characteristics of KSS?

Answer 28

onset before age 20 retinitis pigmentosa at least one of the following: cardiac conduction abnormality, cerebellar ataxia, cerebral spinal protein level above 100 mg/dL

Question 29

What is the main cause of KSS?

Answer 29

mtDNA rearrangements including duplicated mtDNA, deleted mtDNA and insertions

Question 30

Where are ragged red fibers seen in KSS?

Answer 30

skeletal muscle cells

Question 31

What are the characteristics of CPEO?

Answer 31

mild to moderate mitochondrial myopathy, ragged red fibers in skeletal muscle, mtDNA rearrangments ptosis

Question 32

What are the characteristics of LHON?

Answer 32

mitochondrial mutation only affects optic nerve no muscle involvement acute or subacute, bilateral, or central vision lost degeneration of the retinal ganglion cell layer and optic nerve age of onset= 20s to 30s

Question 33

What is the cause of LHON?

Answer 33

mtDNA mutations in coding genes of complex I proteins

Question 34

Mutations affect mtDNA genes encoding complex I proteins are ______ substitutions

Answer 34

single base pair