CFC1 mutations in patients with transposition of the great arteries and double-outlet right ventricle

Am J Hum Genet. 2002 Mar;70(3):776-80. doi: 10.1086/339079. Epub 2002 Jan 17.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cohort Studies
  • Double Outlet Right Ventricle / etiology
  • Double Outlet Right Ventricle / genetics*
  • Exons / genetics
  • Female
  • Growth Substances / genetics*
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Introns / genetics
  • Male
  • Mutation / genetics*
  • Polymorphism, Genetic / genetics
  • RNA Splice Sites / genetics
  • Transposition of Great Vessels / etiology
  • Transposition of Great Vessels / genetics*


  • CFC1 protein, human
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • RNA Splice Sites

Associated data

  • OMIM/300265
  • OMIM/306955
  • OMIM/605194
  • OMIM/605376