Mitochondrial Genetics and Disease Flashcards
What is the function of the mitochondria?
provide cellular energy in the form of ATP for the cell
What are the two ways the mitochondria can provide energy?
Electron transport chain and oxidative phosphorylation
Mitochondria have their own _____
DNA
What are the characteristics of mitochondrial disorders?
clinical variability and age related progression of disease
What does MERRF stand for?
myoclonus epilepsy with ragged red fibers
What does MELAS stand for?
mitochondrial encephalopathy lactic acidosis and stroke like episodes
What does KSS stand for?
Kearns-sayre syndrome
What does CPEO stand for?
chronic progressive external ophthalmoplegia
What does LHON stand for?
leber hereditary optic neuropathy
What is a mitochondrial myopathy?
muscle disease caused by mitochondrial disfunction
What are clinical characteristics of mitochondrial myopathies?
muscle weakness
exercise intolerance
lactic acidosis
neurological signs: mitochondrial encephalopathies
other abnormalities: vomiting, seizures, dementia, stroke like episodes, ptosis, ophthalmoplegia, blindness, cardiomyopathy
What are ragged red fibers?
aggregates of abnormal mitochondria that form red sarcolemmal blotches
Are mitochondria maternally or paternally inherited?
maternally
What is heteroplasmy?
when a mtDNA mutation occurs, a mixture of normal mitochondria and mutant mitochondria occurs in one cell
What is threshold in mitochondrial disease?
when there is too many mutant mitochondria, disease will result
In the ETC, enzyme complexes I to IV oxidize what?
NADH and FADH2
What is complex V?
ATP synthase
Complexes I through V are encoded by what?
nuclear and mitochondrial DNA
Does mtDNA have a repair mechanism?
no
______ mutations in mtDNA tRNA goes lead to MELAS and MERRF
point
mtDNA ______ deletions and rearrangements lead to KSS and CPEO
genome
What are the clinical features of MERRF?
myoclonus (involuntary jerking of the muscle) myoclonic epilepsy ataxia ragged red fibers seizures
90% of MERRF caused by what?
2 mutations of tRNA Lys
85% of MERFF cases due to ___ to ___ mutation in mtDNA tRNA lys one
5% are due to ____ to ____
A to G; G to C
What are characteristics of MELAS?
seizures blindness headaches anorexia recurrent vomiting lactic acidosis ragged red fibers
When is the age of onset for MELAS?
2-10 years
What is the typical cause of MELAS?
A3243B mutation in tRNA leu
What are the characteristics of KSS?
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
What is the main cause of KSS?
mtDNA rearrangements including duplicated mtDNA, deleted mtDNA and insertions
Where are ragged red fibers seen in KSS?
skeletal muscle cells
What are the characteristics of CPEO?
mild to moderate mitochondrial myopathy, ragged red fibers in skeletal muscle, mtDNA rearrangments
ptosis
What are the characteristics of LHON?
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
What is the cause of LHON?
mtDNA mutations in coding genes of complex I proteins
Mutations affect mtDNA genes encoding complex I proteins are ______ substitutions
single base pair
