Lecture 33 - Mitochondrial Genetics and Disease

Question 1

Where do mitochondrial inherited diseases come from and why

L33 S2

Answer 1

-they can only come from the mother as only the mitochondria from the egg are passed down

Question 2

What are the 4 major types of mitochondrial myopathies and what types of mutations lead to each

L33 S7

Answer 2

Point mutations:

• MERRF (myoclonus epilepsy with ragged red fibers)
• MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes

Deletions/rearrangements:

• KSS (Kearns-Sayre syndrome)
• CPEO (chronic progressive external opthalmoplegia)

Question 3

What are some clinical characteristics of mitochondrial myopathies?

L33 S8

Answer 3

• muscle weakness
• exercise intolerance
• lactic acidosis
• neurologic signs (in mitochondrial encephalopathies)

Question 4

What is heteroplasmy and how does it relate to the absence or presence of mitochondrial disorders?

L33 S10-12

Answer 4

Heteroplasmy: mixture of healthy and mutant mitochondria within a cell

• mitochondria replicate and segregate during cell division, this can lead to a large or small amount of mutant mitochondria in a daughter cell
• if enough mutant mitochondria are passed down, above threshold, that cells is diseased
• varying levels of mutant mitochondria may lead to disease at earlier or later ages

Question 5

What are the clinical presentation of MERRF and what is the genetic cause?

L33 S26-27

Answer 5

Clinical presentation:

• myolonus (involuntary muscle jerking)
• myoclonic epilepsy
• ataxia
• ragged red fibers in muscle tissue
• seizures
• dementia

Genetic cause:
-point mutations of the tRNA-lys gene in mtNDNA

Question 6

What is the clinical presentation of MELAS and what is the genetic cause?

L33 S31-32

Answer 6

Clinical presentation:
(Typical onset age 2-10)
-seizures (stroke like symptoms of hemiparesis)
-blindness
-headaches
-anorexia
-recurrent vomiting
-anorexia
-lactic acidosis
-ragged red fibers

Genetic cause:
-point mutation of tRNA-leu gene in mtDNA

Question 7

What is the clinical presentation of KSS and what is the genetic cause?

L33 S34-35

Answer 7

Clinical presentation:

• retinitis pigmentosa (degenerative eye disease)
• cardiac conduction abnormality
• cerebellar ataxia
• increased CSF protein levels

Genetic cause:
-mtDNA arrangements from duplication, deletion, or insertion

Question 8

What is the clinical presentation of CPEO and what is the genetic cause?

L33 S37

Answer 8

Clinical presentation:

• mild to moderate myopathy
• ptosis (drooping eyelid)

Genetic cause:
-mtDNA arrangements