Mitochondrial Inheritance

Question 1

T or F. mtDNA contain no introns and are single-stranded, circular

Answer 1

F. They contain no introns, are circular, and are DOUBLE stranded

Question 2

What complex of the ETC does not have contributions of mtDNA?

Answer 2

Complex 2. Complex 1 contributes the most,

1>4>5>3>2

Question 3

Abnormal expression of mitochondrial diseases is detected more often in tissues/organs with what?

Answer 3

high ATP requirements (Brain, muscle, heart, kidney, )

Question 4

T or F. mtDNA has a higher mutation rate compared to nuclear DNA

Answer 4

T (~10x more)

Question 5

Basis of Mitochondrial Disorders

Answer 5

Result of inherited or spontaneous mutations in mt-DNA or nuclear-DNA which lead to altered functions of the proteins or RNA molecules that normally reside in mitochondria.

Estimate about 1/10000-20,000 (all disorders)

Question 6

What is pleiotropy?

Answer 6

multiple phenotypic effects from a single type mutation

Question 7

T or F. Most mitochondrial diseases affect single organs as opposed to multiple.

Answer 7

F. Only a few (LHON) affect a single organ. Most affect multiple

Question 8

What is Leber’s Hereditary Optic Neuropathy?

Answer 8

Optic nerve atrophy
Sudden loss vision young adults
Most common cause blindness in o/w healthy young men
Generally homoplasmic (some heteroplasmic)
No other tissue typically affected
>50% point mutation in nucleotide 11778 mtDNA, primarily complex I genes

Question 9

T or F. All affected individuals with LHON are homoplasmic.

Answer 9

F. MOST (almost all) are, but some aren’t

Question 10

Mitochondrial Complex IV deficiency (cytochrome C oxidase deficiency)

Answer 10

Autosomal recessive
Failure to thrive
Neurologic:
Optic atrophy, pigmentary retinopathy, ptosis
Senseneural deafness
Cognitive delay, seizures
Basal ganglia abnormaltiy (e.g. ‘Leigh’ disease)

Hypertrophic cardiomyopathy
Muscle hypotonia
Respiratory insufficiency (secondary to muscle weakness)
Renal tubular dysfunction
Hepatomegaly
Anemia

Question 11

Kearns Sayre syndrome

Answer 11

Ophthalmoplegia
Myopathy
Hearing loss
Cardiomyopathy
Cardiac conduction defects
Neuropathy
Ataxia
Failure to thrive (linear growth, hGH)

Question 12

MERRF

Answer 12

Myoclonic epilepsy (with) ragged-red fiber syndrome

Epilepsy, dementia, ataxia, myopathy
Variable expression (heteroplasmic)
Single base changes in a tRNA gene

Question 13

T or F. MERRF is an mtDNA disease and not a nDNA mutation?

Answer 13

T.

Question 14

MELAS

Answer 14

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes
Onset childhood (2-10yr)
Seizures (with stroke-like episodes), headaches
 Anorexia, vomiting, failure to thrive, developmental delay, short stature, limb weakness, deafness
Variable expression (heteroplasmic)
Single base changes in a tRNA gene