CFC1 Mutations in Patients with Transposition of the Great Arteries and Double-Outlet Right Ventricle

• Published in: American journal of human genetics Vol. 70; no. 3; pp. 776 - 780
• Main Authors: Goldmuntz, Elizabeth, Bamford, Richard, Karkera, Jayaprakash D., dela Cruz, June, Roessler, Erich, Muenke, Maximilian
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.03.2002; University of Chicago Press; The American Society of Human Genetics
• Subjects: Base Sequence; Biological and medical sciences; Cardiology. Vascular system; Cohort Studies; Congenital heart diseases. Malformations of the aorta, pulmonary vessels and vena cava; Double Outlet Right Ventricle - etiology; Double Outlet Right Ventricle - genetics; Exons - genetics; Female; Growth Substances - genetics; Heart; Humans; Intercellular Signaling Peptides and Proteins; Introns - genetics; Male; Medical sciences; Mutation - genetics; Polymorphism, Genetic - genetics; RNA Splice Sites - genetics; Transposition of Great Vessels - etiology; Transposition of Great Vessels - genetics; Human; Embryonic development; Pathogenesis; Cardiovascular disease; Congenital disease; Genetic determinism; Genetic disease; Vascular disease; Gene; Heart disease; Double outlet right ventricle; Mutation; Transposition of the great vessels
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/339079

Recent investigations identified heterozygous CFC1 mutations in subjects with heterotaxy syndrome, all of whom had congenital cardiac malformations, including malposition of the great arteries. We hypothesized that a subset of patients with similar types of congenital heart disease—namely, transposition of the great arteries and double-outlet right ventricle, in the absence of laterality defects—would also have CFC1 mutations. Our analysis of the CFC1 gene in patients with these cardiac disorders identified two disease-related mutations in 86 patients. The present study identifies the first autosomal single-gene defect for these cardiac malformations and indicates that some cases of transposition of the great arteries and double-outlet right ventricle can share a common genetic etiology with heterotaxy syndrome. In addition, these results demonstrate that the molecular pathway involving CFC1 plays a critical role in normal and abnormal cardiovascular development.