The more common form of transposition of the great arteries, dextro-looped TGA, consists of complete inversion of the great vessels, so that the aorta incorrectly arises from the right ventricle and the pulmonary artery incorrectly arises from the ... The more common form of transposition of the great arteries, dextro-looped TGA, consists of complete inversion of the great vessels, so that the aorta incorrectly arises from the right ventricle and the pulmonary artery incorrectly arises from the left ventricle. (In the less common type of TGA, levo-looped TGA, the ventricles are inverted instead) (Goldmuntz et al., 2002). This creates completely separate pulmonary and systemic circulatory systems, an arrangement that is incompatible with life. Patients with TGA often have atrial and/or ventricular septal defects or other types of shunting that allow some mixing between the circulations in order to support life minimally, but surgical intervention is always required. For a discussion of genetic heterogeneity of dextro-looped transposition of the great arteries, see 608808.
Because CFC1 mutations had been identified in patients with heterotaxy syndrome (605376), all of whom had congenital cardiac malformations, including malposition of the great arteries, Goldmuntz et al. (2002) hypothesized that a subset of patients with similar types ... Because CFC1 mutations had been identified in patients with heterotaxy syndrome (605376), all of whom had congenital cardiac malformations, including malposition of the great arteries, Goldmuntz et al. (2002) hypothesized that a subset of patients with similar types of congenital heart disease--namely, dextro-looped transposition of the great arteries and double-outlet right ventricle, in the absence of laterality defects--would also have CFC1 mutations. Analysis of the CFC1 gene in 86 patients with these cardiac disorders identified 2 disease-related mutations (605194.0003 in DORV and 605194.0004 in DTGA2). Goldmuntz et al. (2002) stated that this was the first identification of an autosomal single-gene defect for these cardiac malformations and pointed out that the results indicate that some cases of transposition of the great arteries and double-outlet right ventricle share a common genetic etiology with heterotaxy syndrome. Furthermore, the molecular pathway involving CFC1 plays a critical role in normal and abnormal cardiovascular development.