The direct congenital Gerbode defect was a rare type of ventricular septal defect (VSD) causing a communication between the left ventricle (LV) and right atrium (RA). In this case, only LV-to-right ventricle (RV)shunt was found preoperatively. But in operation, the defect was located at the interventricular septum between the tricuspid (TV) and mitral valves (MV) where the shunt was from LV to right atrium (RA) and septal TV dysplasia was found. The shunt might be LV-to-RA and the blood flow into the RV through the defect of TV. This article discussed why the preoperative ultrasound misdiagnosed this type of shunt and reviewed the literature of Gerbode defect.

Genome sequencing(GS) has been applied in the diagnosis of global developmental delay(GDD)/intellectual disability(ID). However, the performance in those with inconclusive results from chromosomal microarray analysis(CMA) and exome sequencing(ES) is unknown. We recruited 100 pediatric GDD/ID patients from multiple sites in China from February 2018 to August 2020 for GS. Patients have received at least one genomic diagnostic test prior to enrollment. Reanalysis of CMA/ES data was performed. The yield of GS was calculated and explanations for missed diagnoses by CMA/ES were investigated. Clinical utility was assessed by interviewing the parents by phone. The overall diagnostic yield of GS was 23%. Seven families could have been solved with reanalysis of ES data. 13 families were missed by previous CMA/ES due to improper method. Three remained unsolved after ES reanalysis due to allele dropout, complex variants missed by ES, and a CNV in untranslated regions. Follow-up of the diagnosed families revealed that nine families experienced changes in clinical management, including identification of targeted treatments, cessation of unnecessary treatment, and considerations for family planning. GS demonstrated high diagnostic yield and clinical utility in this cohort of undiagnosed GDD/ID patients, detecting a wide range of variant types of different sizes in a single workflow.

The Gerbode defect is a special type of ventricle septum defect causing a communication between the left ventricle and right atrium. In this article, we present a rare case of 2-year-old congenital Gerbode defect. The location of this defect was special, just at the interventricular septum between the tricuspid and mitral valve. She underwent the closure of the defect with an autologous pericardial patch in station of mild hypothermic cardiopulmonary bypass.

Atrioventricular septal defects (AVSD) are a complicated subtype of congenital heart defects for which the genetic basis is poorly understood. Many evidences have demonstrated that transcription factor SOX7 which can interact with GATA4 plays a pivotal role in the cardiovascular development. The critical role of GATA4 in the morphogenesis of atrioventricular septum implies SOX7 a potential involvement of AVSD. However, whether SOX7 variants are involved in the pathogenesis of AVSD needs to be explored. Through target sequencing, we identified three rare variants c.40C>G, c.542G>A, and c.743C>T of SOX7 in 100 sporadic non-syndromic AVSD Chinese Han patients. All mutant sites were highly conserved in mammals. The mRNA and protein levels of SOX7 variants were altered compared with those of the wildtype. Moreover, SOX7 overexpression promoted the expression of GATA4 in human umbil-ical vein endothelial cells. Chromatin immunoprecipitation assay uncovered that SOX7 could directly bind to the region of GATA4 promoter. Luciferase assays demonstrated that SOX7 activated GATA4 promoter and the variants impaired the transcriptional activity of SOX7. Furthermore, the variants of SOX7 altered the regulation to the activity of GATA4 on its target genes. Our studies provide evidence that deleterious variants in SOX7 are potential contributors to human AVSD and provide novel insights into the etiology of AVSD.