Objective: Congenital diaphragmatic hernia (CDH) is a rare abnormality with highly heterogeneous genetic causes. This study investigated chromosomal and monogenic abnormalities in fetal CDH patients and evaluated the efficacy of chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) for genetic diagnosis. The clinical features of the patients were also evaluated.
Methods: We evaluated the genetic and clinical data of 51 prenatally diagnosed fetuses with CDH. CMA was performed for every patient. If CMA did not yield diagnostic results, the samples were subjected to WES.
Results: Compared with fetuses with isolated CDH (n = 42), those with non-isolated CDH (n = 9) presented a higher genetic diagnostic rate (22.2% vs. 2.4%). The overall diagnostic yield was 5.9%, comprising 3.9% from chromosomal microarray analysis (CMA) and an additional 2.0% from whole exome sequencing (WES). CMA identified (1) mosaic trisomy 18 in a patient with isolated CDH; and (2) 4q terminal deletion syndrome in a patient with non-isolated CDH. WES identified a novel missense mutation, PLS3 c.1763A > G, associated with X-linked CDH in a patient with non-isolated CDH and a family history of recurrent CDH.
Conclusion: Genetic testing should be offered for all fetuses with CDH, regardless of whether the cases are isolated or non-isolated. WES should be considered if CMA fails to provide a diagnostic result, particularly in patients with non-isolated CDH and a family history of recurrent CDH.
Keywords: chromosomal microarray analysis; congenital diaphragmatic hernia; diagnostic variant; prenatal diagnosis; whole‐exome sequencing.
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