SH3 domain binding glutamate-rich protein (SH3BGR), which contains a highly conserved SH3 binding motif and a glutamic acid-rich domain at the COOH terminal [48], was initially identified to be involved in heart morphogenesis, and hence, in the pathogenesis of congenital heart disease (CHD) in Down syndrome (DS) [49]. This evidence concerns the gene SH3BGR and Down syndrome.