GMDS Intragenic Deletions Associate with Congenital Heart Disease including Ebstein Anomaly

Ebstein anomaly is a rare heterogeneous congenital heart defect (CHD) with largely unknown etiology. We present 6-year-old girl anomaly, atrial septum defect, hypoplastic right ventricle, and persistent left superior vena cava who has de novo intragenic ~403 kb deletion of the GDP-mannose 4,6-dehydratase (GMDS) gene. GMDS located on chromosome 6p25.3 encodes rate limiting enzyme in GDP-fucose synthesis, which used to fucosylate many proteins, including Notch1, plays critical role during mammalian cardiac development. The locus sporadically been associated (large deletion) tetralogy Fallot (small deletion). Given its function association CHD, we hypothesized that loss-of-function of, or alterations in, could play development anomaly. collected further 134 cases screened them for genomic aberrations locus. No additional were identified. In conclusion, describe Together previous reports, this second case suggests deletions be cause disease, particular