Huntington's Disease ICD Flashcards
Caused by a trinucleotide repeat expansion located on the short arm of chromosome 4
Huntington’s Disease
Poly glutamine protein that forms aggregates leading to Huntington’s
Huntington Protein
What is the prevalence of Huntington’s in North America?
1/10,000
An autosomal dominant inheritance with almost 100% penetrance
Huntington’s
What is the clinical triad of Huntington’s?
Chorea, Dimentia, and psychiatric/behavioral disorder
Irregular, purposeless movements and writhing
Chorea
Individuals symptomatic for Huntington’s have an expansion of CAG repeats in the HD protein coding region of chromosome 4. How many repeats indicates Huntington’s?
Anything >39
Non-HD individuals have up to
36 CAG repeats
The HD gene is located on the short arm of chromosome 4 at position
16.2
The laboratory test for Huntington’s can be produced on any cell with a
Nucleus
What is the range of CAG repeats considered to be “asymtomatic but mutable?”
27-35 repeats
-Normal is 26
Protein partners of huntingtin have a role in
transcription regulation, intracellular trafficking
and
Cytoskeletal organization
Many huntingtin binding proteins have a role in
Endocytosis
Interacts with at least 70 known proteins
Huntingtin
Highly conserved protein that has a central role in cell function and broad subcellular distribution
Huntingtin
Associated with membrane compartments of synaptic vesicles, recycling endosomes
-There’s an abundance in the ER and Golgi
Huntingtin
Normal Huntingtin has a role in membrane trafficking in the cytoplasm and in axonal transport. It is also found in the
Nucleus
Rehearse the two potential outcomes with the patient prior to gene testing. Gene test results are always disclosed in person never by phone.
Presymptomatic Testing
The major difficulty encountered with presymptomatic testing is
Anxiety
Documented genetic counseling is required before you can get
Presymptomatic testing
What is the wait time for the test results from Huntington’s?
2-4 weeks
Prenatal and Preimplantation genetics allow a couple with at least one affected to have a child with a guarantee of
No Huntington’s
How does the prenatal and preimplantation genetics work?
Produce fertilized eggs in vitro. Use PCR to identify CAG repeat numbers. Implant embryo with normal CAG repeat values
Huntington’s Disease protein inhibits transcription of the normal Huntington gene. Normal Huntington’s protein is essential to cell survival, deficiency causes
Cell death
Form insoluble aggregates in the nucleus and cause cells to die
Polyglutamine fragments
Have been implicated by elevated lactate content in HD brains on MRI spectroscopy.
Mitochondrial Injury
A naturally occurring biological pathway in which
small, double-stranded RNA molecules suppress gene expression in an exquisitely sequence-specific manner
RNA interference (RNAi)
Exogenous manipulation of RNAi is being explored as a powerful method of silencing disease-causing genes in
Incurable neurological disorders
Uses RNA-guided enzymes to snip out or add segments of DNA to a cell. Could be used to stop Huntington’s
CRISPR
The drug, IONIS-HTTRx, is a so-called antisense drug
that inhibits the expression of the huntingtin gene and
therefore reduces the production of
Huntingtin
Anti-sense drugs can not cross the
Blood-brain barrier
What do anti-sense drugs do?
Block translation
What are the issues that arise from genetic testing in HD?
Financial, Ethical, Legal, and Social (FELSI) issues
Genetic testing of minors and fetuses, disclosure of testing information to family members at risk for disease, and potential misuse of genetic information by employers or insurance companies are examples of
FELSI
Has been model disease to evaluate the
ethical, legal, financial and social issues
associated with adult onset genetic disease
testing.
Huntington’s
