Diagnostic contribution of conventional and molecular karyotyping in congenital diaphragmatic hernia related copy number variations.

OBJECTIVE

Congenital Diaphragmatic Hernia (CDH) results from defects in the developing diaphragm and is characterized by herniation of abdominal contents into the thoracic cavity. Notably, CDH is linked to elevated morbidity and mortality rates due to its association with pulmonary hypoplasia. Copy number variations (CNVs) are significant contributors to the etiology of CDH. We aimed to investigate the involvement of new candidate CNVs in CDH etiology and the effectiveness of karyotyping and array-based Comparative Genomic Hybridization (a-CGH) in CDH diagnosis.

MATERIALS AND METHODS

Among the 10,536 prenatal cases, 198 cases with CDH were enrolled in this study. Statistical analyses were performed to investigate the possible correlation between CDH type, maternal age, and chromosomal anomaly ratio. Chromosomal analysis was conducted on 188 cases with appropriate material. Consequently, an a-CGH study was executed on 90 cases with normal karyotype results and high-quality DNA material.

RESULTS

Chromosomal anomaly frequency was significantly higher (p = 0.0001) in complex than in isolated CDH. In 13.3 % of the cases, various chromosomal anomalies including triploidy, aneuploidy, and those indicating certain syndromes such as Pallister-Killian, Cat-Eye, Turner, and Klinefelter were detected with karyotyping. In nine cases, three pathogenic CNVs including 17q12 microdeletion, 15q11.2 microdeletion, Xq27.1 microduplication, and seven additional CNVs with unknown significance, were identified with the a-CGH study.

CONCLUSION

Our study results significantly support the involvement of chromosomal anomalies and CNVs in CDH etiology. Moreover, our findings revealed new candidate regions for CDH and strengthened the CDH correlation of known CNVs, which may provide a resource for future studies.