The Role of MLPA in Detecting Syndromic Submicroscopic Copy Number Variations in Normal QF-PCR Miscarriage Specimens.

Area of Science:

• Genetics
• Reproductive Medicine

Background:

• Miscarriage is a common global event with diverse etiologies.
• Identifying the cause of pregnancy loss is crucial for future reproductive planning.
• Genetic abnormalities are a significant factor, particularly in early pregnancy loss.

Purpose of the Study:

• To determine the rate of copy number variations (CNVs) in spontaneous miscarriage samples.
• To evaluate the utility of MLPA following negative QF-PCR results.
• To identify pathogenic CNVs in products of conception.

Main Methods:

• DNA extraction from product-of-conception tissue.
• Utilized MLPA (SALSA® MLPA® Probemix P245) to detect 31 microdeletion/microduplication syndromes.
• Analyzed 84 successfully tested samples.

Main Results:

• Copy number variations (CNVs) were identified in 11 samples (13.1%).
• Duplications were found in 9.5% and deletions in 3.6% of samples.
• Only three CNVs (3.6%) were confirmed as pathogenic, including DiGeorge-2 syndrome, Rett syndrome, and 2q23.1 microduplication syndrome.

Conclusions:

• MLPA assays demonstrate limited effectiveness in detecting additional chromosomal abnormalities in miscarriage cases.
• Further genetic testing (e.g., aCGH/SNP microarray) is often necessary to confirm CNV pathogenicity.
• The diagnostic yield of MLPA for secondary chromosomal abnormalities in miscarriages appears restricted.