title: CFC1 mutations in patients with transposition of the great arteries and double-outlet right ventricle.
abstract: 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.
authors.affiliation: Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Goldmuntz
authors.forename: Richard
authors.initials: R
authors.lastname: Bamford
authors.forename: Jayaprakash D
authors.initials: JD
authors.lastname: Karkera
authors.forename: June
authors.initials: J
authors.lastname: dela Cruz
authors.forename: Erich
authors.initials: E
authors.lastname: Roessler
authors.forename: Maximilian
authors.initials: M
authors.lastname: Muenke
mesh_terms: D001483:Base Sequence; D015331:Cohort Studies; D004310:Double Outlet Right Ventricle / Q000209:etiology / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007438:Introns / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D014188:Transposition of Great Vessels / Q000209:etiology / Q000235:genetics*
chemical_list: C491268:CFC1 protein, human; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D022821:RNA Splice Sites