ORIGINAL ARTICLE

Pediatric Cardiology

, Volume 27, Issue 6, pp 695-698

First online:

Mutations in the EGF-CFC Gene Cryptic Are an Infrequent Cause of Congenital Heart Disease

  • Cemil ÖzcelikAffiliated withMax-Delbrück-Center for Molecular MedicineDepartment of Cardiology, University Hospital, Campus Virchow-Klinikum und Berlin-Buch, Charite, Universitätsmedizin, Helios-Kliniken Email author 
  • , Nana Bit-AvragimAffiliated withMax-Delbrück-Center for Molecular MedicineDepartment of Cardiology, University Hospital, Campus Virchow-Klinikum und Berlin-Buch, Charite, Universitätsmedizin, Helios-Kliniken
  • , Anna PanekAffiliated withMax-Delbrück-Center for Molecular MedicineDepartment of Cardiology, University Hospital, Campus Virchow-Klinikum und Berlin-Buch, Charite, Universitätsmedizin, Helios-Kliniken
  • , Ursula GaioAffiliated withGSF-Institute for Stem Cell Research
  • , Christian GeierAffiliated withDepartment of Cardiology, University Hospital, Campus Virchow-Klinikum und Berlin-Buch, Charite, Universitätsmedizin, Helios-Kliniken
  • , Peter E. LangeAffiliated withDepartment of Pediatric Cardiology, German Heart Institute Berlin
  • , Rainer DietzAffiliated withDepartment of Cardiology, University Hospital, Campus Virchow-Klinikum und Berlin-Buch, Charite, Universitätsmedizin, Helios-Kliniken
  • , Maximilian G. PoschAffiliated withMax-Delbrück-Center for Molecular MedicineDepartment of Cardiology, University Hospital, Campus Virchow-Klinikum und Berlin-Buch, Charite, Universitätsmedizin, Helios-Kliniken
  • , Andreas PerrotAffiliated withDepartment of Cardiology, University Hospital, Campus Virchow-Klinikum und Berlin-Buch, Charite, Universitätsmedizin, Helios-Kliniken
    • , Brigitte StillerAffiliated withDepartment of Pediatric Cardiology, German Heart Institute Berlin

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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.

Keywords

Cryptic CFC1 Congenital heart disease Atrial septal defect Polymorphism