title: Is diagnosing cardio-facio-cutaneous (CFC) syndrome still a challenge? Delineation of the phenotype in 15 Polish patients with proven mutations, including novel mutations in the BRAF1 gene.
abstract: Cardio-facio-cutaneous (CFC) syndrome is characterized by a variable degree of developmental delay and congenital anomalies, including characteristic facial, cardiac, and ectodermal abnormalities. It is caused by activating mutations in the Ras/mitogen-activated protein kinase (MAPK) signaling pathway. In, however, approximately 10%-30% of individuals with a clinical diagnosis of CFCS, no mutation of the causative gene is found. Therefore, clinical studies in patients with the CFCS spectrum are valuable. To investigate the phenotypic spectrum and molecular diversity of germline mutations affecting genes encoding serine/threonine kinases, a group of 15 children and young adults with a diagnosis of CFCS was screened. We documented three novel mutations in the BRAF gene and correlated clinical findings with causative mutations in the BRAF or MEK1/MEK2 genes.
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Ciara
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Pelc
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Jurkiewicz
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland; Department of Child and Adolescent Psychiatry, The Medical University of Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Kugaudo
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland; Department of Paediatrics, Medical University of Warsaw, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Gieruszczak-Białek
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland; Department of Paediatrics, Medical University of Warsaw, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Skórka
authors.affiliation: Podlaskie Center of Clinical Genetics, Białystok, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Posmyk
authors.affiliation: Clinical Genetics Mastermed, Białystok, Poland; Department of Pediatric Neurology and Rehabilitation, Medical University of Białystok, Białystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Jakubiuk-Tomaszuk
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Cieślikowska
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Krystyna H
authors.initials: KH
authors.lastname: Chrzanowska
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland. Electronic address: jezela@gmail.com.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jezela-Stanek
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Krajewska-Walasek
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D004476:Ectodermal Dysplasia / Q000175:diagnosis / Q000235:genetics*; D019066:Facies; D005183:Failure to Thrive / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000235:genetics*; D048370:MAP Kinase Kinase 2 / Q000235:genetics*; D008297:Male; D009154:Mutation; D010641:Phenotype; D011044:Poland / Q000453:epidemiology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C482128:MAP2K2 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human
keywords: BRAF; CFC; Cardio-facio-cutaneous syndrome; Genotype–phenotype; KRAS; MEK1; MEK2; Novel mutation