Testing for Genetic Disorders Flashcards
What are the prenatal testing options and is it risky? invasive?
- Screening tests
- Assess risk but not definitive diagnostic test eg
maternal serum testing for Down syndrome - Non invasive, low risk tests
- Diagnostic tests
- Where test for a specific chromosomal or
genetic abnormality eg gene mutation analysis
for cystic fibrosis - Invasive test, carries some risk
Clinical Indications for Prenatal Testing
- Concerns regarding a Single gene disorders
* Family history
* Both parent carriers of an autosomal recessive
disorder eg cystic fibrosis
* Female carrier of a sex linked disorder eg
haemophilia (X chromosome linked)
* One parent has an autosomal dominant disorder - Considered at risk of a constitutional
chromosomal disorder
* Older mother pregnant
* Previous child with significant developmental or
other disorder
* Exposure to chemical or other toxic agent
* Abnormal screening test result
What are the 3 screening strategies
- timing of each, risks, invasive
- Ultrasound scan of pregnancy
- At 8 weeks to check dates, confirm number of
babies - At 18 weeks detailed scan for anomalies can be
done eg anencephaly, cardiac abnormalities - Safe procedure – no risk to mother or fetus
- Maternal Serum Testing
* Trimester 1 blood test
– 9 - 13 weeks
– B-HCG, PAPP-A
– With ultrasound scan
- Trimester 2
– 14 – 18 weeks
– Blood test alone
– AFP, β-hCG, unconjugated oestriol (uE3), Inhibin A
- Nuchal Translucency
* Measure by ultrasound 10–13 weeks pregnancy
* Non invasive test
* Combine with maternal serum testing to
increase sensitivity and specificity for Down
syndrome screening
How good is the screening methods in second trimester for trisomy?
- maternal blood (alone in second trimester) vs fetal NT (first semester) and maternal
Screening in the second trimester by maternal age and maternal serum testing can identify 50-75% of trisomy 21 pregnancies with a false positive rate of 5%
Screening by fetal NT in the first trimester and maternal serum biochemistry reported a detection rate of trisomy 21 of 85-90% with false positive rate of 5%
If there is a high risk based on prediction (pedigree) then what happens next?
May lead to a specific diagnostic test eg
- amniocentesis
-Chorionic Villus Sampling
These all collect fetal cells for further anaylsis (FISH and karyotype analysis)
Chorionic Villus Sampling
-when can you do it
purpose
risk of miscarriage
- 10 – 12 weeks of pregnancy
- Obtain fetal cells – analyze chromosomes or DNA (via vaginal)
- Risk of miscarriage < 1%
Amniocentesis
When can u do it
Purpose
miscarriage risk
- 15-16 weeks of pregnancy
- Collect fluid which contains fetal cells via needle into stomach
- May need to culture cells before analysis
- Miscarriage risk < 1%
Amniocentesis vs CVS
Drawing of process
Lecture Slide
Non typical diagnostic test:
Fetoscopy and umbilical cord blood sampling
- when can u do it
miscarriage risk
Purpose
- Performed late in pregnancy
- Miscarriage risk 2 – 10%
- Obtain fetal blood which can be analyzed for:
Karyotype and FISH
Gene mutation analysis
Metabolic disorders
Anaemia
What are the new strategies for prenatal diagnosis
- Non invasive prenatal testing (NIPT)
- Pre-implantation genetic testing (PGD)
NIPT: Non invasive prenatal testing
- what is it
Detection of cell free fetal DNA in the maternal plasma
- Parallel sequecing of total DNA present in maternal plasma. Alignment of sequencing reads to human genome sequence and determination of relative chromsome representation
- Non invasive screening test
for aneuploidies - Confirm with diagnostic test
eg amniocentesis
Lecture Slide for diagram
Process of testing
- Everyone gets prenatal screening
- Ultrasound, maternal serum testing, Nuchal treanslucency - If high risk: NIPT
fetal DNA from maternal plasma - If pos then diagnositic testing offererd
- CVS
-Amniocentesis
-karotyping
What is Preimplantation Genetic Diagnosis
(PGD) process
- IVF cycle to make many eggs
- eggs are fertilised to make embryos
- embryos anaylsed for genetic defects (using FISH)
- Only healthy embryos are injected into uterus
- Genetically healthy baby
Issues to consider with prenatal testing
- Not comprehensive testing
- Only test for common chromosome disorders
- Single gene disorders
– Need to know mutation - Risk of error eg clerical,
laboratory testing - Risk (small) to fetus
- Not morally or ethically acceptable to all
- Not all parents want to know
Potential benefits of prenatal
testing
- Reassurance when results normal
- Psychological preparation for arrival of
affected baby - Advance warning for medical team
- Provision of additional information for couple
where termination is an option
