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Are CNVs Associated with Miscarriage?


  • Chromosomal abnormalities are the most common cause of early pregnancy loss but role of submicroscopic copy-number variations (CNVs) remains unclear
  • Wang et al. (Ultrasound in Obstetrics & Gynecology, 2019) sought to identify potential miscarriage-associated submicroscopic CNVs as well as candidate genes for miscarriage


  • Study design
    • Over a 5-year period, fresh miscarriage specimens were analyzed using
      • Quantitative fluorescent polymerase chain reaction (qfPCR) and sequencing
      • Chromosomal microarray analysis
  • Frequency of recurrent submicroscopic CNVs were compared between miscarriage cases and a published control cohort
  • Potential candidate genes
    • Genes were prioritized based on whether miscarriage-associated CNVs disrupted critical gene regions


  • 5,180 miscarriage specimens obtained | 5,003 (96.6%) did not have significant maternal-cell contamination
    • Clinically significant chromosomal abnormalities were identified in 59.1%
      • Single aneuploidies accounted for majority of these cases (43.6%) with trisomies accounting for the biggest group  
      • Partial aneuploidies (large CNVs) were noted in 3.8% of cases
      • Microdeletions and microduplications were seen in 2.7%
    • Of these abnormal cases, 97.4% could have been detected using standard G-banding cytogenetic technique (size of abnormality >10 Mb)
  • 3 recurrent submicroscopic (<10 Mb) CNVs were significantly more frequent in miscarriage cases
    • 22q11.21 | 2q37.3 | 9p24.3p24.2
  • 44 critical regions of large CNVs (14 deletions and 30 duplications) appeared to recur in the miscarriage specimens
    • Large deletions were seen most commonly in chromosomes 8, 4 and 1
    • Large duplications were seen most commonly in chromosomes 8, 7 and 11
  • Candidate genes: 309 genes were identified as possible miscarriage related genes based on gene-prioritization analysis


  • The authors of this study identified potential genes and CNVs associated with miscarriage
  • Due to new technologies, the authors stress the importance of continuing to analyze CNVs in the study of miscarriage
  • The authors state that

22q11.21 microdeletion is a miscarriage‐causing locus, and that early embryonic death could be caused by major heart malformations resulting from the 22q11.21 deletion.

Learn More – Primary Sources:

Systematic analysis of copy‐number variations associated with early pregnancy loss