Abstract
Background
Mutations in the SETD5 gene lead to the autosomal dominant disorder termed Mental retardation type 23. Limited clinical reports have made it challenging to comprehensively delineate the clinical outcomes and mutation spectrum associated with this gene.
Case presentation:
In this study, a fetal case presenting an ostium primum atrial septal defect, a presumed upper ventricular septal defect was identified through fetal cardiac ultrasound. Following this discovery, an in-depth genetic assessment, encompassing whole exome sequencing, was executed on the fetus and both parents to pinpoint potential genetic origins. From the exome data, a previously undocumented variant (exon21: c.3601_3605del: p. W1201Efs*2) in the SETD5 gene (NM_001080517.3) surfaced. Lineage analysis validated this as a de novo variant. This mutation disrupts the gene's open reading frame, consequently affecting protein functionality. This is the first prenatal diagnosis of a fetus with a SETD5 mutation, advancing the time of diagnosis while broadening our understanding of the gene's mutation spectrum and clinical manifestations.
Conclusions
Our study confirms that congenital heart disease, including atrial and ventricular septal defects, is a prenatal clinical feature caused by mutations in this gene. Fetal cardiac ultrasound can be used as a means of early screening for such disorders, and the importance of prenatal whole-exome sequencing technology was emphasized.