Novel compound heterozygous mutation in causes complex congenital heart disease.

Congenital heart disease (CHD) is the most common birth defect, affecting 2‑8% of newborns, with a marked impact on neonatal health. In the present study, the parents of a fetus diagnosed with CHD were recruited to investigate the genetic causes of this condition. Whole exome sequencing was conducted on tissue obtained from the fetus. A compound heterozygous mutation in the dynein axonemal heavy chain 9 () gene, comprising c.11176C>T (p.Arg3726Trp) and c.3743+1G>T, was identified. The c.11176C>T mutation has been previously reported as likely pathogenic, and c.3743+1G>T is a novel mutation. Sanger sequencing was employed for pedigree analysis. In addition, bioinformatics analyses were performed to predict the pathogenicity of the identified mutations, while and minigene analyses were conducted to examine the splicing patterns associated with the splicing mutation. Software predictions and minigene analysis revealed that the c.3743+1G>T mutation leads to abnormal splicing. According to the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines, the two identified mutations were classified as likely pathogenic. The present study identified the pathogenic variants in the affected family and expanded the mutation spectrum of the gene. It also provided a foundation for genetic counseling and reproductive intervention.