20.05.10 Application of NGS for prenatal diagnosis

Question 1

What percentage of prenatal cases will be undiagnosed after QF-PCR, karyotyping, arrayCGH

Answer 1

60%

Question 2

Main use of NGS in prenatal setting

Answer 2

NIPD/NIPT

Question 3

Considerations of using NGS in prenatal setting

Answer 3

• Rapid turn around time required
• Minimal amounts of starting material
• High sensitivity/ specificity
• Tight guidelines for reporting

Question 4

Other uses of NGS in prenatal setting

Answer 4

• Identifying chromosomal aneuploidy
• Haplotype based NIPD for X-linked and AR disorders.
• Single gene disorders diagnostics
• WES for fetuses with sonographic abnormalities

Question 5

Pros and cons of WES for diagnostic testing in prenatal setting

Answer 5

• Pro: all coding genes tested so could diagnose almost any single gene disorder
• Con: TAT is too long, lack of phenotype in fetus, incidental findings, VUS

Question 6

Example of a study that used WES in prenatal setting

Answer 6

Drury et al. 2015

• WES in 24 fetuses with ultrasound abnormalities, but normal cytogenetically.
• Either proband only or trios
• 21% had definitive diagnoses

Conclusions:

• Inability to fully cover exome hinders interpretation
• needs fast data interpretation and parental samples available

Question 7

NGS in prenatal setting according to National genomic test directory

Answer 7

-Standard testing for cases of fetal anomalies is
-Aneuploidy
-Microarray
-NGS using a large panel associated with fetal anomalies.
All classed as core tests, so should be available through all GLHs.