TNR Disorders Flashcards
Genetic anticipation
Through generations, disease presents @ earlier age and with greater severity
In HD, how many repeats to be affected?
> 39
HD expansion transmitted primarily by?
Father
Where is the TNR for HD?
Coding region (Exon 1)
3 phenotypes of huntingtons
Neurodegenerative chorea, behavior changes, dementia
Mechanism of HD
Misfolded protein aggregates from extra glutamines causes cell dysfunction
Fragile X Syndrome - TNR location?
5’ UTR
Fragile X Syndrome - # repeats for normal, PM, FM?
Normal - 200
Fragile X Syndrome - Mechanism of PM disease?
PM - RNA toxicity
Fragile X Syndrome - Mechanism of FM disease?
Promoter methylation; no FMR protein
What is function of FMR protein?
It is an RNA - Binding protein, brings in RISC, acts as translational regulator
Fragile X Syndrome - Type of inheritance?
XLR
Fragile X Syndrome - PM phenotype (2)
Premature ovarian failure before 40
Tremor ataxia
Fragile X Syndrome - FM phenotype (4)
Severe cognitive defect, autism, altered facies, large testes
Fragile X Syndrome - affects males or females primarily?
Males (XLR)
Friedrich’s ataxia - full mutation repeats?
> 200
Friedrich’s ataxia - TNR location?
1st intron (no splicing, RNA gets degraded)
Friedrich’s ataxia - Mechanism of disease?
MRNA transcript degredation, loss of frataxin protein, mitochondrial dysfunction.
Friedrich’s ataxia - Clinical phenotype
Hereditary ataxia (neurologic dysfunction), cardiomyopathy, diabetes mellitus
(Heart, brain, pancreatic beta cells)
Myotonic Dystrophy 1 - TNR locationn
3’ UTR
Myotonic Dystrophy 1 - inheritance pattern
AD
Myotonic Dystrophy 1 - mild, moderate, severe repeats
Mild 50-150,
Moderate 100-1000
Severe >1,000
Expansion transmission of Myotonic Dystrophy 1 -
Expansion of >1,000 only from mother, expansion in oocyte.
Myotonic Dystrophy 1 - Mechanism of disease
Sequestering of RNA splicing proteins
Myotonic Dystrophy 1 - clinical phenotype
Adult onset muscle weakness and wasting, cataracts, arrythmias, NO COGNITIVE IMPAIRMENT
