European journal of medical genetics, vol.64, no.7, pp.104215, 2021 (SCI-Expanded)
Congenital diaphragmatic hernia (CDH) is a serious life-threatening birth defect characterized by abnormal development in the muscular or tendinous portion of the diaphragm during embryogenesis. Despite its high incidence, the etiology of CDH hasn't been fully understood. Genetic factors are important in pathogenesis; however, few single genes have been definitively implicated in human CDH. SLIT1, SLIT2, and SLIT3 (slit guidance ligand) are three human homologs of the drosophila Slit gene. They interact with roundabout (Robo) homolog receptors to affect cell migration, adhesion, cell motility, and angiogenesis and play important roles in cell signaling pathways including the guidance of axons. In this report, we presented dizygous twin babies with CDH related to the SLIT3 gene variant. Previous studies showed that Slit3 null mice had congenital diaphragmatic hernias on or near the ventral midline portion of the central tendon. This is the first report of homozygous SLIT3 variant associated with CDH in humans.