A French Approach to Test Fetuses with Ultrasound Abnormalities Using a Customized Microarray as First-Tier Genetic...

Area of Science:

• Prenatal genetics
• Medical genomics
• Reproductive medicine

Background:

• Cytogenetic microarray analysis is a primary genetic test for postnatal evaluation of developmental disabilities and birth defects.
• Its prenatal application is limited due to challenges in assessing the clinical significance of copy number variants (CNVs).
• This is particularly relevant in France, where pregnancy termination can occur at any gestational stage.

Purpose of the Study:

• To evaluate the utility of a customized cytogenetic microarray for prenatal diagnosis in fetuses with ultrasound anomalies.
• To assess the rate of pathogenic CNVs, including cryptic variants, detectable by this method.
• To determine the impact of this strategy on genetic counseling challenges.

Main Methods:

• A 15-month study investigated 382 fetuses with ultrasound anomalies using a customized microarray.
• The microarray was designed to avoid CNVs that pose genetic counseling difficulties.
• Common aneuploidies were excluded, and array comparative genomic hybridization (aCGH) was performed.

Main Results:

• Pathogenic CNVs were identified in 5.3% (20/374) of fetuses, with 2.1% (8/374) being cryptic.
• In ongoing pregnancies (300 cases), pathogenic CNVs were found in 6% (18/300), including 2% (6/300) cryptic variants.
• Only 0.6% (2/300) of detected CNVs presented genetic counseling challenges.

Conclusions:

• The customized microarray strategy enhances the detection of genomic imbalances in prenatal settings.
• This approach significantly reduces ethical issues related to genetic counseling.
• It demonstrates added value for prenatal diagnosis and management of fetal anomalies.