Human genetics of d-transposition of the great arteries

Abstract

Dextro-transposition of the great arteries (d-TGA) is one of the rare congenital heart diseases (CHD) which benefits from early neonatal diagnosis because d-TGA requires rapid postnatal catheter procedure. In that respect, detecting parental genetic predisposing factors would contribute to focusing prenatal echographical attention to the early detection of d-TGA cases. A high male to female ratio and a high recurrence risk of d-TGA in the context of heterotaxy suggest the impact of genetic factors although familial cases of d-TGA are exceptional. Since the late 1990s, a growing list of genes and chromosomal regions was associated with d-TGA among which the ZIC3 gene. Although this gene is located on the X chromosome, ZIC3 (Zic family member 3) does not explain the male preponderance in d-TGA. d-TGA causal genes are involved in many different cellular pathways and can be provisionally sorted in two groups: those which disrupt the function of the embryonic node cilia and those which are downstream of this major embryological process of lateralization. Many more genes or gene factors remain to be discovered in d-TGA and related CHD because only a small percentage of d-TGA is yet genetically resolved.