title: Mutations in the EGF-CFC gene cryptic are an infrequent cause of congenital heart disease.
abstract: Cryptic (CFC1), a member of the epidermal growth factor-Cripto/FRL-1/Cryptic (EGF-CFC) gene family, is involved in the evolutionarily conserved establishment of left-right lateral asymmetry. Inactivation of Cfc1 in mice results in laterality defects and complex cardiac malformations. Similarly, mutations in the human CFC1 gene have been identified in patients with heterotaxy syndrome. The cardiac defects in humans resemble those in mice lacking Cfc1. We postulated that some patients with isolated cardiac malformations could also have mutations in the CFC1 gene. Our analysis of the CFC1 gene in 167 patients with congenital heart disease revealed a novel A145T missense variant in 3 patients with type II atrial septal defect. Furthermore, we found the previously characterized R78W polymorphism in another patient with type II atrial septal defect. However, the A145T sequence alteration was also identified in 3 controls, suggesting that this variant is a polymorphism. We conclude that CFC1 variants could be a rare cause of congenital heart disease in patients without laterality defects.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Robert-Roessle-Strasse 10, 13125, Berlin, Germany. oezcelik@mdc-berlin.de
authors.forename: Cemil
authors.initials: C
authors.lastname: Ozcelik
authors.forename: Nana
authors.initials: N
authors.lastname: Bit-Avragim
authors.forename: Anna
authors.initials: A
authors.lastname: Panek
authors.forename: Ursula
authors.initials: U
authors.lastname: Gaio
authors.forename: Christian
authors.initials: C
authors.lastname: Geier
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lange
authors.forename: Rainer
authors.initials: R
authors.lastname: Dietz
authors.forename: Maximilian G
authors.initials: MG
authors.lastname: Posch
authors.forename: Andreas
authors.initials: A
authors.lastname: Perrot
authors.forename: Brigitte
authors.initials: B
authors.lastname: Stiller
mesh_terms: D004815:Epidermal Growth Factor / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000235:genetics*; D006343:Heart Septal Defects / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D020125:Mutation, Missense; D016415:Sequence Alignment
chemical_list: C491268:CFC1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor