Copy number variations analysis in a cohort of 47 fetuses and newborns with congenital diaphragmatic hernia

Prenat Diagn. 2022 Dec;42(13):1627-1635. doi: 10.1002/pd.6268. Epub 2022 Nov 26.


Objectives: The congenital diaphragmatic hernia (CDH), characterized by malformation of the diaphragm and lung hypoplasia, is a common and severe birth defect that affects around 1 in 4000 live births. However, the etiology of most cases of CDH remains unclear. The aim of this study was to perform a retrospective analysis of copy number variations (CNVs) using a high-resolution array comparative genomic hybridization (array-CGH) in a cohort of fetuses and newborns with CDH.

Methods: Forty seven fetuses and newborns with either isolated or syndromic CDH were analyzed by oligonucleotide-based array-CGH Agilent 180K technique.

Results: A mean of 10.2 CNVs was detected by proband with a total number of 480 CNVs identified based on five categories: benign, likely benign, of uncertain signification, likely pathogenic, and pathogenic. Diagnostic performance was estimated at 19.15% (i.e., likely pathogenic and pathogenic CNVs) for both CDH types. We identified 11 potential candidate genes: COL25A1, DSEL, EYA1, FLNA, MECOM, NRXN1, RARB, SPATA13, TJP2, XIRP2, and ZFPM2.

Conclusion: We suggest that COL25A1, DSEL, EYA1, FLNA, MECOM, NRXN1, RARB, SPATA13, TJP2, XIRP2, and ZFPM2 genes may be related to CDH occurrence. Thus, this study provides a possibility for new methods of a positive diagnosis.

MeSH terms

  • Comparative Genomic Hybridization / methods
  • DNA Copy Number Variations
  • Fetus
  • Hernias, Diaphragmatic, Congenital* / genetics
  • Humans
  • Infant, Newborn
  • Retrospective Studies
  • Transcription Factors / genetics


  • Transcription Factors