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Pre-Implantation Genetic Testing for Aneuploidy on a Semiconductor Based Next-Generation Sequencing Platform
Published on: August 17, 2022
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Exploring the factors affecting classification and reporting of uncertain prenatal microarray findings, using a
Rachel Michaelson-Cohen1, Liat Sheelo Salzer2, Dana Brabbing-Goldstein2
1Faculty of Medicine, Medical Genetics Institute, Shaare Zedek Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.
Prenatal Diagnosis
|February 14, 2024
Summary
Geneticists showed significant disagreement classifying prenatal copy number variants (CNVs). Factors like variant type and specialist experience influenced reporting and testing recommendations for these genetic conditions.
Area of Science:
- Genetics
- Medical Genetics
- Prenatal Diagnosis
Background:
- Discrepancies in classifying and reporting copy number variants (CNVs) are prevalent across laboratories.
- Limited research exists on factors influencing the management of prenatal CNVs.
- A pilot study using a
- Purpose_of_the_Study
- Main_Methods
- Main_Results
- Conclusions
Purpose of the Study:
- To investigate factors influencing the classification and reporting of prenatal copy number variants (CNVs).
- To examine the impact of geneticist specialization and experience on CNV management recommendations.
- To identify key elements for developing a clinical consensus algorithm for CNV analysis.
Main Methods:
- Fifteen medical doctor geneticists classified ten prenatally diagnosed CNVs (>1Mb) of uncertain significance (VUS).
- CNVs encompassed OMIM-morbid genes and were inherited from healthy parents.
- Geneticists evaluated factors affecting classification, reporting obligations, and recommendations for invasive testing or preimplantation genetic testing (PGT).
Main Results:
- CNV classification varied widely: 10.7% likely benign, 74.7% VUS, 8.7% likely pathogenic, 6.0% pathogenic.
- Classification discrepancies were higher for deletions than duplications.
- Reporting (84.0%), invasive testing (29.3%), and PGT (32.4%) recommendations were influenced by CNV classification, variant type, and geneticist specialization/experience.
Conclusions:
- Dosage, family phenotype, and geneticist factors significantly impact CNV classification and reporting.
- Understanding these factors is crucial for developing standardized clinical management algorithms.
- This pilot study highlights the need for consensus in prenatal CNV interpretation and reporting.
