Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome

Abstract

Cardio-facio-cutaneous (CFC) syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. It phenotypically overlaps with Noonan and Costello syndrome, which are caused by mutations in PTPN11 and HRAS, respectively. in 43 individuals with CFC, we identified two heterozygous KRAS mutations in three individuals and eight BRAF mutations in 16 individuals, suggesting that dysregulation of the RAS-RAF-ERK pathway is a common molecular basis for the three related disorders.Tohoku Univ, Sch Med, Dept Med Genet, Sendai, Miyagi, JapanCatholic Univ, Ist Genet Med, Rome, ItalyHop Robert Debre, APHP, Dept Genet, Paris, FranceOsaka Med Ctr, Dept Planning & Res, Osaka, JapanRes Inst Maternal & Child Hlth, Osaka, JapanInst Child Hlth, Clin & Mol Genet Unit, London, EnglandAcad Med Ctr, Dept Pediat, Amsterdam, NetherlandsUniv Essen Gesamthsch, Inst Human Genet, Essen, GermanyUNIFESP, Ctr Med Genet, São Paulo, BrazilKanagawa Childrens Med Ctr, Div Med Genet, Yokohama, Kanagawa, JapanSaitama Childrens Med Ctr, Div Med Genet, Saitama, JapanGreat Ormond St Hosp Sick Children, London, EnglandPitie Salpetriere Univ Hosp, Dept Genet, Paris, FranceUniv Hosp, Dept Genet, Angers, FranceAzienda Osped Univ G Martino, Dipartimento Sci Pediat Med & Chirurg, Unita Operat Complessa Patol Neonatale & Terapia, Messina, ItalyUniv Ryukyus, Sch Med, Dept Med Genet, Okinawa, JapanYokohama City Univ, Grad Sch Med, Dept Human Genet, Yokohama, Kanagawa, JapanTohoku Univ, Comprehens Res & Educ Ctr Planning Drug Dev & Cli, Cent COE Program 21, Sendai, Miyagi, JapanUNIFESP, Ctr Med Genet, São Paulo, BrazilWeb of Scienc