MM18 - Aspects of Clinical Genetics (i)
elements of genetic counselling
patient understands diagnosis, prognosis, implications, mode of inheritance, transmission risk, available options
NON-DIRECTIVE (patient's choice)
pre + posting testing, with continuous follow-up
referrals to support groups/psychosocial support
Genetic testing
cascade testing: extending test to other family members
for either presymptomatic disease or carrier identification
why do patients want one?
family planning
future planning
remove uncertainty
mostly restricting to inherited diseases (chromosomal abnormalities, monogenic conditions
not useful for complex-common disease (not entirely genetic)
Lab genetic tests
karyotyping, CGH, FISH
for large deletions/duplications (e.g. Down's syndrome)
Biochemical tests
fast, cheap
don't assay actual DNA (don't identify genomic mutations)
e.g. heel prick test
doesn't find carriers
for PKU, sickle cell anaemia (HbS instead of HbA)
direct genetic tests
NGS, Sanger sequencing
best resolution (sequences bases)
for any disease with a known mutation
slow, expensive
sometimes fragments too small to detect large deletions/duplications
e.g. for CF (can be due to compound mutation, i.e. same gene, 2 alleles, 2 mutations) + Duchenne muscular dystrophy
Prenatal diagnosis
do with advanced maternal age (less reliable dysjunction)
same lab methods, different sampling
start with non-invasive (maternal blood contains small amount of human DNA), if it comes back +ve confirm with invasive
invasive tests
chorionic villus sampling
amniocentesis
1-3% miscarriage risk
is risk of procedure > risk for foetal abnormality?
Down's Syndrome prenatal test
1st trimester (12wk scan)
non-invasive
look for subcut oedema of foetal neck on ultrasound
maternal serum proteins
test for PAPPA (pregnancy-associated plasma protein A) + free beta HCG
if 12wk test +ve, do 2nd trimester screen
maternal serum proteins: alpha-fetoprotein, hCG, unconjugated estriol
if 2nd trimester screen +ve, do invasive confirmatory test
new: harmony prenatal test
non-invasive
analyses cell free foetal (cff) DNA in maternal blood using NGS
biopsy of chorionic villi via catheter
guided using transcervical/transabdominal ultrasound
can be done @ 8-10 wks
yields lots of tissue (culture not necessary)
doesn't detect alphafetoprotein (neural tube defects)
1% increase in miscarriage risk
10-20ml of amniotic fluid withdrawn under transabdominal ultrasound guidance
culture + assay for alpha-fetoprotein, enzymes, viruses + karyotype
can be done @ 4-6wks
0.2% increase in miscarriage risk
ethical issues
informed consent
testing for conditions where the prognosis can't be altered
abortion decisions
moral issues
do Drs warn patient's family? No
do Drs warn employer? No unless condition will affect it (e.g. seizures in a pilot)
designer embryos