Somayyeh Heidargholizadeh G, Gulec Cagri, Bulut Gulnihal, Kalelioglu Ibrahim Halil, Has Recep, Sivrikoz Tugba Sarac, Kalayci Tugba, Selcuk Bilge Ozsait, Karaman Birsen
Department of Medical Genetics, Institute of Health Sciences, Istanbul University, Istanbul, Türkiye.
Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye.
Taiwan J Obstet Gynecol. 2025 Jul;64(4):678-686. doi: 10.1016/j.tjog.2025.03.015.
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.
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.
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.
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.
先天性膈疝（CDH）是由发育中的膈肌缺陷引起的，其特征是腹腔内容物疝入胸腔。值得注意的是，由于CDH与肺发育不全相关，其发病率和死亡率较高。拷贝数变异（CNV）是CDH病因的重要因素。我们旨在研究新的候选CNV在CDH病因中的作用以及核型分析和基于芯片的比较基因组杂交（a-CGH）在CDH诊断中的有效性。
在10536例产前病例中，本研究纳入了198例CDH病例。进行统计分析以研究CDH类型、母亲年龄和染色体异常率之间的可能相关性。对188例有合适材料的病例进行了染色体分析。因此，对90例核型结果正常且DNA材料质量高的病例进行了a-CGH研究。
复杂型CDH的染色体异常频率显著高于孤立型CDH（p = 0.0001）。在13.3%的病例中，通过核型分析检测到各种染色体异常，包括三倍体、非整倍体以及那些表明某些综合征的异常，如帕利斯特-基利安综合征、猫眼综合征、特纳综合征和克兰费尔特综合征。在9例病例中，通过a-CGH研究鉴定出3个致病CNV，包括17q12微缺失、15q11.2微缺失、Xq27.1微重复，以及另外7个意义不明的CNV。
我们的研究结果有力地支持了染色体异常和CNV参与CDH病因。此外，我们的发现揭示了CDH的新候选区域，并加强了已知CNV与CDH的相关性，这可能为未来的研究提供资源。
