A novel homozygous variant of induced cardiac malformation and neurodevelopmental abnormality: case report and literature review.

Background: Congenital heart disease (CHD) represents the most widespread congenital birth defect among neonates worldwide, leading to substantial expenses and contributing significantly to premature death caused by birth defects. Despite the significance of CHD, research on its etiology remains limited and has failed to provide substantial evidence for the molecular basis of the disease. With the advancement of next-generation sequencing (NGS), genetic screening has become increasingly accessible, offering a greater capability for identifying potential genetic variants associated with CHD.

Case Presentation: Exome sequencing and variant analysis of were performed to obtain genetic data, and clinical characteristics were determined. A complex and severe form of CHD, comprising a persistent truncus arteriosus type I, ventricular septal defect, right aortic arch, as well as critical neurodevelopmental delay and neurological dysfunction, was observed in a patient. This proband presented global muscle hypotonia and a significant delay in gross and fine motor development. Cranial computed tomography scanning showed the presence of bilateral apical, occipital, and temporal subdural effusions; slightly wider bilateral lateral ventricles and annular cisterns; and bilateral cerebral hemispheric parenchyma atrophy. Upon genetic analysis of the patient, a novel homozygous mutation was identified in the gene. The mutation, c.1336_1339DEL, was found to be homozygous and resulted in a frameshift mutation, causing a p.L447Vfs9 amino acid change. This mutation led to the deletion of a TCTC sequence from positions 1336 to 1339 in the gene, changing leucine to valine at amino acid 447 and introducing a stop codon after the ninth amino acid. This structural deletion in the protein resulted in the loss of gene function.

Conclusion: This case report presents a newly discovered variant site in the gene and reinforces the relationship between molecular function and differentiation of mesoderm and ectoderm. Furthermore, our findings broaden the spectrum of variants in the gene and contribute to advancing the genetic understanding of CHD.