Identification of chromosomal abnormalities in miscarriages by CNV-Seq

Area of Science:

• Genetics
• Reproductive Biology
• Bioinformatics

Background:

• Recurrent miscarriages are a significant concern in reproductive health.
• Understanding the genetic underpinnings of miscarriages is crucial for improving outcomes.
• Copy number variants (CNVs) are increasingly recognized as a cause of pregnancy loss.

Purpose of the Study:

• To analyze chromosomal abnormalities in miscarriages using copy number variants sequencing (CNV-Seq).
• To identify potential genes and pathways associated with miscarriage.
• To provide guidance for subsequent pregnancies based on genetic findings.

Main Methods:

• Enrolled 580 miscarriage cases with clinical data and CNV-Seq results.
• Performed bioinformatic analyses on validated pathogenic CNVs (pCNVs).
• Utilized Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis.

Main Results:

• A positive detection rate of 61.87% for chromosomal abnormalities was observed in 577 evaluable cases.
• 470 variants were identified in 357 cases, with 65.32% classified as pathogenic.
• Numerical abnormalities increased with maternal age, while structural abnormalities decreased; TP53, CTNNB1, UBE3A, EP300, SOX2, ATM, and MECP2 were highlighted as potentially significant genes.

Conclusions:

• Chromosomal abnormalities, including microdeletions and duplications, are significant contributors to miscarriages.
• Identified pathogenic CNVs and associated genes provide a basis for understanding miscarriage etiology.
• Findings offer potential guidance for birth health in future pregnancies.