Huntington's disease Flashcards
what is huntington’s disease (HD)
- progressive neurodegenerative disorder => dementia
- shrinkage of brain & loss of neurons
- 35-50yo get symptoms
HD patients can show:
a) homogenous expression OR
b) biallelic HD (B-HD)
what does that mean?
a) homo: >36 CAG repeats in BOTH alleles
b) B-HD: 1 mutated allele (>=40 CAG repeats) & the other CAG expanded allele (>=27)
molecular pathophysiology of HD
expansion of unstable polymorphic
trinucleotide (CAG)n repeat in exon 1 of the HTT gene (chrom 4) => translates into extended polyglutamine tract in huntingtin (HTT)
determine the phenotype based on the number of CAG repeat
a) <=26 repeat
b) 27-35
c) 36-39
d) >=40
a) normal
b) normal, but risk offspring may get HD
c) reduced penetrance, may not get HD, risk offspring might
d) full penetrance =get HD
(genetic testing on embryos) What is the meaning of these
a) PGT-A
b) PGT-M
c) PGT-SR
d) HLA matching
a) -A: test for aneuploidy (presence of extra chromosome)
b) -M: test for monogenic & single gene disorders
c) -SR: test for structural chrom. rearrange,ents
d) harvest stem cells of newly born child that’s HLA compatible w/ a child who needs BM transplant,
Describe the triplet primed repeat assay
- used for apparent homozygosity and large expansions
- uses a FWD, RVS primer & random primer to bind in b/w
Describe the pathogenic mechanism of HD
the extended HTT protein causes
- aggregation in nucleus => intranulcear inclusion = dysregulates transcription
- aggregation in cytoplasm = impaired proteiostasis network => synaptic dysfunction, mitochondrial toxicity
Explain the process of predictive testing & counselling
- Enquiry of risk in family & explain protocol
1st sesh: genetic counselling & provide info
2nd: person’s motives, impact on family, possible psychological rxns
3rd: revise points in 2nd, coping assesment & prepare for results
4th: test results & counselling
5th: check up on coping & feelings @ 1 wk
* HRisk: contact at 18 months
* LRisk: conatct at 1 & 12 months
