Copy-number variation and false positive prenatal aneuploidy screening results

Area of Science:

• Genetics
• Prenatal Diagnostics
• Molecular Biology

Background:

• Noninvasive prenatal screening (NIPS) for fetal aneuploidy using cell-free DNA (cfDNA) offers high accuracy but is limited by low positive predictive values.
• The underlying causes of false positive NIPS results remain largely unknown, hindering test interpretation.

Observation:

• Four pregnancies with discordant NIPS results were investigated.
• In two cases, discordant results were linked to the presence of maternal duplications on chromosome 18.

Findings:

• Maternal copy-number variants (CNVs) are identified as a potential cause for false positive NIPS results.
• Specific large maternal duplications on chromosome 18 were implicated in discordant NIPS findings.

Implications:

• Understanding maternal CNVs can improve the accuracy and interpretation of NIPS results.
• This research may lead to refined NIPS protocols and better genetic counseling for expectant parents.