Genetic principles through neurodegenerative disease (dominant inheritance) Flashcards
Huntington’s disease is what type of condition
autosomal dominant
expansion of what trinucleotide in HD
CAG - exon 1 in Huntington gene
alleles of 36-39 CAG resets show
incomplete penetrance - many carriers remaining asymptomatic into old age
alleles of 40 or more show
complete penetrance - meaning if inherit you will develop
In HD repeats most commonly show an expansion when inherited from the father. Longer CAG repeats are associated with earlier onset and increased severity of symptoms at what level can you have juvenile onset
over 60
The mutant form of the huntingtin protein is found in aggregates and inclusions within the brain – a classic example of a gain of function effect. This has a toxic effect on the neurons of the central nervous system and leads to cell death and neurodegeneration
what other disease are like this
Other TNR disorders with expanded runs of glutamines in different proteins can also cause HD like symptoms (e.g. Spinocerebellar ataxia type 17 and Dentatorubral-pallidoluysianatrophy).
In HD the loss of GABAergic neurons in the striatum affects the indirect pathway leading to an increase in motor activity
symptoms
hyperkinesia clumsy restlessness twitch chorea attention span and memory short depression
treatment for Huntington’s
tetrabenazine
neuroleptics - block dopamine
only symptoms can be treated
what is anticipation
increasing in severity or decreased age onset observed in successive genes
what is normal CAG repeat
26 and under
what is huntigtons CAG repeat
over the 36
age of onset of Huntington’s
35-44
how many CAG repeats for juvenile
60
duration of HD
after diagnosis 10-18 years
when can you get a pre-symptomatic/predicitve genetic test?
only when you have either 50-25% chance of getting the disease with proof - at least 1 family member
only 1/4 go for test though of those at risk
minro not tested until 18
pre-impaltntion test in embryo too.
