Molecular Genetics in Prenatal Diagnosis Flashcards
When the problem isn't aneuploidy
What are the indications for molecular testing in the prenatal setting?
- familiy history of a known familial variant
- parent(s) known carrier of a genetic disease
- ultrasound anomalies
What is needed by the lab to test the fetus for autosomal recessive or X-linked conditions that the parents are carriers of?
- blood samples from the carriers as positive control samples
- copy of carrier screening results is not enough
- lab wants to know what exactly they are looking for and to check that they’re able to detect it
When is targeted variant analysis appropriate and what else is always included in this testing?
- when you know exactly which genetic variation is in the family, this is the most cost effective option
- lab just looks at exactly what you request
- will also have chromosomal anlysis done - it’s just always done
If you want to order single-gene testing based on an US finding, you’ll have to do what first?
Tiered testing. Begin with chromosome anlysis and microarray. This is due to likelihood and dealing with insurance wnting to pay for higher yield, less expensive test. Basically, need to rule out aneuploidies first.
Most labs require a new psoitive control sample for gene testing. Can we get around this?
Nope. You will need US anomalies for testing without a positive control sample. Even if the only other person with the variant had testing at that lab and is deceased.
Under New York State Public Health Law (Article 5, Title V, Section 574) and regulations
(Part 58- 1.10 (g) of 10NYCRR), laboratories performing testing for ________________ must hold a New York State clinical laboratory permit or have test
request approval for specific tests.
any specimens collected
in the State of New York
Testing laboratories must discard all samples submitted from NYS within ________ unless the patient provides signed permission for the sample to be kept longer than that
60 days
The Clinic for Special Children—clinic and laboratory in PA specializing in
genetic disorders affecting the …
Plain People
What is a downside of using The Clinic?
it is targeted variant testing and may miss the ultra-rare diagnosis
WES and WGS are “phenotype driven” and should only ever be considered in the presence of ___________________.
ultrasound anomalies
the vast majority of labs will not accept a prenatal sample in the absence of ultrasound anomalies. It makes variant interpretation much more challenging.
Post test counseling for WES/WGS
If AR and a healthy parent has both variants we know they were inherited in ____ and are
not related to the phenotype
cis
Case study of TTN variant
VUS in father that seems pathogenic but remains a VUS to this day. Research paper writtten on case. Family had IVF and healthy daughter
Amnio is as close to ________ as we can get.
100%
Confined placental mosaicism is an issue for CVS and effects ________________ only, not _______________.
aneuploidy only, not single gene.
How accurate is CVS?
About 98%
