Human Genetics of Atrial Septal Defect

Abstract

Although atrial septal defects (ASD) can be subdivided based on their anatomical location, an essential aspect of human genetics and genetic counseling is distinguishing between isolated and familiar cases without extracardiac features and syndromic cases with the co-occurrence of extracardiac abnormalities, such as developmental delay. Isolated or familial cases tend to show genetic alterations in genes related to important cardiac transcription factors and genes encoding for sarcomeric proteins. By contrast, the spectrum of genes with genetic alterations observed in syndromic cases is diverse. Currently, it points to different pathways and gene networks relevant to the dysregulation of cardiomyogenesis and ASD pathogenesis. Therefore, this chapter reflects the current knowledge and highlights stable associations observed in human genetics studies. It gives an overview of the different types of genetic alterations in these subtypes, including common associations based on genome-wide association studies (GWAS), and it highlights the most frequently observed syndromes associated with ASD pathogenesis.

Keywords: ACTC1; ASD; ASD 2; Atrial septal defect; Atrioventricular septum defects; BRAF; CDK13; CHARGE syndrome; CHD4; CHD7; Cardio-facio-cutaneous syndrome; Cardiomyogenesis; DHCR7; Familial ASD; G6PC3; GATA4GATA binding protein (GATA)GATA4; Genome-wide association studies; Holt-Oram syndrome; Isolated ASD; KMT2D; Kabuki syndrome; MAP2K1; MAP2K2; MYH6Myosin heavy chain (MYH)MYH6; Mowat-Wilson syndrome; NKX2-5; Noonan syndrome; PEX7; PFO; PTPN11; Patent foramen ovale; Primum atrial septal defects; RBM10; Rhizomelic chondrodysplasia punctata; Secundum atrial septal defects; Sifrim-Hitz-Weiss syndrome; Sinus venosus defects; Smith–Lemli–Opitz syndrome; Sporadic ASD; Syndromic ASD; TARP syndrome; TBX20T-box (TBX)TBX20; TBX5; ZEB2; endoMT.