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FISH for Pre-implantation Genetic Diagnosis
Published on: February 23, 2011
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Clinical experience with a single-nucleotide polymorphism-based non-invasive prenatal test for five clinically
Clinical Genetics
|July 12, 2017
Summary
Single-nucleotide polymorphism (SNP)-based non-invasive prenatal testing (NIPT) shows improved accuracy for detecting microdeletion syndromes like 22q11.2 deletion syndrome. High-depth resequencing significantly enhances the positive predictive value and reduces false positives in prenatal screening.
Area of Science:
- Genetics
- Prenatal Diagnostics
- Molecular Biology
Background:
- Single-nucleotide polymorphism (SNP)-based non-invasive prenatal testing (NIPT) is a valuable tool for detecting submicroscopic chromosomal abnormalities.
- Microdeletion syndromes, such as 22q11.2 deletion syndrome and others affecting chromosomes 1p36, cri-du-chat, Prader-Willi, and Angelman, are associated with severe clinical manifestations.
Purpose of the Study:
- To evaluate the performance of SNP-based NIPT for specific microdeletion syndromes.
- To compare the effectiveness of an original screening protocol with a revised protocol involving high-depth resequencing for high-risk calls.
- To estimate the prevalence of these microdeletion syndromes within a referral population.
Main Methods:
- Retrospective analysis of 80,449 referrals for 22q11.2 deletion syndrome and 42,326 referrals for 1p36, cri-du-chat, Prader-Willi, and Angelman microdeletion syndromes.
- Comparison of an original SNP-based NIPT protocol with a revised protocol utilizing reflexive high-depth sequencing for elevated-risk results.
- Estimation of minimal prevalences for the studied microdeletion syndromes.
Main Results:
- The revised protocol significantly increased the positive predictive value (PPV) for 22q11.2 deletion syndrome from 15.7% to 44.2% and for other microdeletions from 5.2% to 31.7%.
- The false-positive rate (FPR) for 22q11.2 deletion syndrome decreased from 0.33% to 0.07%, and for other microdeletions from 0.56% to 0.07% with the revised protocol.
- Minimal prevalences were estimated at 1 in 1255 for 22q11.2 deletion syndrome and 1 in 1464 for the combined group of other microdeletions.
Conclusions:
- Microdeletion syndromes are relatively common in the analyzed referral population.
- SNP-based NIPT performance, particularly its positive predictive value and false-positive rate, is substantially improved by implementing high-depth resequencing for high-risk cases.
- The findings support the utility of enhanced SNP-based NIPT protocols for accurate prenatal detection of microdeletion syndromes.
