Prenatal Arrays

Question 1

What are the challenges of prenatal arrays?

Answer 1

• finding that is uncertain
• neuro-susceptibility locus where there is evidence of unaffected individuals
• might find a pathogenic variant which isn’t related to the reason for referral but will impact the health of the child in the future (and even the family).

Question 2

What qualifies for a prenatal array?

Answer 2

• fetal abnormality detected by scan
• increased NT >3.5mm (between 11 and 14 weeks)
• a fetus with a sex chromosome aneuploidy which is unlikely to explain the scan findings.

Question 3

What should always be reported?

Answer 3

Any variant that will inform the management of the pregnancy:

• high penetrance neuro-susceptibility loci that are associated with a severe phenotype
• neuro-susceptibility loci which are associated with an incidence of scan anomalies (this may help future scanning)
• unsolicited pathogenic finding that will affect welfare of child and possibly parents such as BRCA deletion?
• dystrophin deletion in a female fetus.

Question 4

Give an example of a couple of things you wouldn’t report…

Answer 4

• deletion of a recessive gene which cannot be linked to the presenting phenotype
• 15q11.2 NIPA del/dup BP1-BP2 (Prader-Willi/Angelmans region which extends to BP3)

Question 5

Give an example of a neuro-susceptibility loci that would get reported…

Answer 5

16p11.2 deletion, both proximal (TBX6) and distal (SH2B1)

Question 6

What are the limitations of arrays?

Answer 6

• may not always detect mosaicism although SNP track might give you a clue
• can’t detect balanced rearrangements
• can’t detect mutations
• can detect UPD caused by isodisomy but not by heterodisomy
• overall spacing is 1.8kb and a 10 probe minimum call gives an effective resolution of 18kb which is 18,000 bases. However, some regions are more densely tiled than others where they are known to be implicated in disorders of clinical significance.

Question 7

What particular challenge does a neuro-susceptibility loci pose?

Answer 7

Difficult/almost impossible to predict the extent to which, if at all, the resultant child would be affected.