Congenital heart disease (CHD) is the most common noninfectious cause of death during the neonatal stage. T‐box transcription factor 1 (TBX1) is the main genetic determinant of 22q11.2 deletion syndrome (22q11.2DS), which is a common cause of CHD. Moreover, ferroptosis is a newly discovered kind of programmed cell death. In this study, the interaction among TBX1, miR‐193a‐3p, and TGF‐β2 was tested using quantitative reverse transcription polymerase chain reaction (qRT‐PCR), Western blotting, and dual‐luciferase reporter assays. TBX1 silencing was found to promote TGF‐β2 messenger ribonucleic acid (mRNA) and protein expression by downregulating the miR‐193a‐3p levels in H9c2 cells. In addition, the TBX1/miR‐193a‐3p/TGF‐β2 axis was found to promote ferroptosis based on assessments of lipid reactive oxygen species (ROS) levels, Fe²⁺ concentrations, mitochondrial ROS levels, and malondialdehyde (MDA) contents; Cell Counting Kit‐8 (CCK‐8) assays and transmission electron microscopy; and Western blotting analysis of glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2‐related factor 2 (NRF2), heme oxygenase‐1 (HO‐1), NADPH oxidase 4 (NOX4), and acyl‐CoA synthase long‐chain family member 4 (ACSL4) protein expression. The protein expression of NRF2, GPX4, HO‐1, NOX4, and ACSL4 and the level of MDA in human CHD specimens were also detected. In addition, TBX1 and miR‐193a‐3p expression was significantly downregulated and TGF‐β2 levels were high in human embryonic CHD tissues, as indicated by the H9c2 cell experiments. In summary, the TBX1/miR‐193a‐3p/TGF‐β2 axis mediates CHD by inducing ferroptosis in cardiomyocytes. TGF‐β2 may be a target gene for CHD diagnosis and treatment in children.

Short rib‑polydactyly syndrome type III (SRPS3) is a lethal perinatal skeletal disorder consisting of polydactyly and multi‑system organ abnormalities. To further assess the pathogenicity of two pairs of compound heterozygotes and to search for novel molecular etiology, X‑rays and hematoxylin and eosin staining were conducted in three cases: Two retrospective samples and a newly identified patient with SRPS3. In addition, next‑generation sequencing was used to evaluate a fetus with SRPS3. Typical radiological features of the three cases included a long, narrow thorax with short ribs, shortened long bones, spurs at the metaphysis of the long bones and congenital bowing of the femurs. The present study also observed atypical histopathological changes, together with the absence of proliferation and abundance of retaining cartilage in the primary spongiosum. In addition, two novel compound heterozygous variants were identified in the dynein cytoplasmic 2 heavy chain 1 (DYNC2H1) gene of the fetus: NM_001080463.1, c.6591_6593delTGG (chr11:103055738‑103055740); NM_001080463.1, c.7883T>C (chr11:103070000). The findings of the present study provided further confirmation of the pathogenicity of two compound heterozygous variants in two retrospective samples and identified novel compound heterozygous variants. These findings may improve our knowledge of the histopathological and radiological changes in patients with SRPS3 and the relative effects of DYNC2H1 variants. The findings of the present study may facilitate the clinical and molecular diagnosis of SRPS3.

In the current study, one case of COG5‑CDG involving a Chinese male patient with severe neurological symptoms, who had previously been misdiagnosed with congenital gyrus malformation, is described. A clinical investigation was performed and targeted next‑generation sequencing (NGS) was used to identify COG5 variants in the patient and his family. PCR and Sanger sequencing were performed for the verification of NGS results. The patient showed severe central and peripheral neurological symptoms, while only mild symptoms were reported in a previous reported case, in which different mutations were involved. The reported patient carried the frameshift mutation c.330delT (p.V111Lfs*22), and a missense mutation c.2324 C>T (p.P775L) in the COG5 gene. The c.330delT (p.V111Lfs*22) variant is a novel mutation, while c.2324 C>T (p.P775L) has previously been reported. Inheriting one variant from each of his parents, the current case report furthers the understanding of genotype‑phenotype correlations in COG5‑CDG.