genetics Flashcards
36-39 repeats may….
have reduced penetrance
circa 30% chance of not manifesting the disease but can still transmit to offspring
describe anticipation
condition worsens in successive generations,
tendancy for repeats to expand in successive generations,
true for other trinucleotide repat disorders
but not a common feature of most dominant conditions
what rating scale can be used to measure huntington’s disease decline and clinical performacne
unified huntingtons disease rating scale
what must be fulfilled before genetic testing is carried out
has the test been requested by a neurologist or neuropsychiatrist with relevant experience,
has the patient been appropriately counselled about the implications of tesing and possible test outcomes,
patient must agree on two sessions two months apart.
has the neurological examinationr revealed evidence of motor symptoms,
have the patient’s family or caregiver been included in discussions about the diagnostic test and hereditary implications of HD,
has informed consent been given,
what are some implications of genetic testing in HD
no disease modifying treatment so use cautiously,
no coercion and decision must be stable over time,
insurance implications,
prenatal diagnosis?
Describe the repeat length of HD
~80 infantile onset
~60 juvenile onset 50%
40 unequivocally abnormal
36-39 reduced penetrance
28-35 new mutations may arise
Below 27 unequivocally normal
ACMG statement 1998
what main types of mutations can occur?
loss of function:
enzyme does not work,
gain of function: protein does something it shouldn’t do,
STOP codon mutations,
Deletions, Duplications,
Splice site mutations, expansion trinucleotides,
non-sense mutations,
mis sense mutations
what is a non-sense mutation?
out of frame deletion produces a stop codon,
RNA detaches from ribosome and is eliminated
what is a mis-sense mutation?
may or may not be pathological,
changes the type of amino acid,
disrupts the active site,
not seen in large number of individuals
why should caution be administerd when interpreating the result of a genetic test
mutations may not be pathological,
may simply be polymorphisms
what is lacking for HD diagnostic testing?
specific guidelines
what genes have been linked to early onset alzheimers
presenillin 1, APP, Presenillin 2
which genes have been linked to FTD
MAPT ,
GRN (progranulin),
C9orf72
genetic testing in FTD
pathology may guide testing dependent on protein inclusions,
counselling before testing,
uptake between 7 & 17% in dutch study
