title: Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome.
abstract: Noonan syndrome (NS) and cardio-facio-cutaneous (CFC) syndrome are autosomal dominant disorders characterized by heart defects, facial dysmorphism, ectodermal abnormalities, and mental retardation. There is a significant clinical overlap between NS and CFC syndrome, but ectodermal abnormalities and mental retardation are more frequent in CFC syndrome. Mutations in PTPN11 and KRAS have been identified in patients with NS and those in KRAS, BRAF and MAP2K1/2 have been identified in patients with CFC syndrome, establishing a new role of the RAS/MAPK pathway in human development. Recently, mutations in the son of sevenless gene (SOS1) have also been identified in patients with NS. To clarify the clinical spectrum of patients with SOS1 mutations, we analyzed 24 patients with NS, including 3 patients in a three-generation family, and 30 patients with CFC syndrome without PTPN11, KRAS, HRAS, BRAF, and MAP2K1/2 (MEK1/2) mutations. We identified two SOS1 mutations in four NS patients, including three patients in the above-mentioned three-generation family. In the patients with a CFC phenotype, three mutations, including a novel three amino-acid insertion, were identified in one CFC patient and two patients with both NS and CFC phenotypes. These three patients exhibited ectodermal abnormalities, such as curly hair, sparse eyebrows, and dry skin, and two of them showed mental retardation. Our results suggest that patients with SOS1 mutations range from NS to CFC syndrome.
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Narumi
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan. aokiy@mail.tains.tohoku.ac.jp.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Niihori
authors.affiliation: Department of Cardiovascular Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakurai
authors.affiliation: Department of Genetics, Hôpital Robert Debré (APHP), Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Cavé
authors.affiliation: Department of Genetics, Hôpital Robert Debré (APHP), Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.affiliation: Department of Clinical Genetics, Seirei Hamamatsu General Hospital, Hamamatsu, Japan.|Nishio Family Clinic, Hamamatsu, Japan.
authors.forename: Kimio
authors.initials: K
authors.lastname: Nishio
authors.affiliation: Division of Medical Genetics, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohashi
authors.affiliation: Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
authors.affiliation: Department of Planning and Research, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Division of Medical Genetics, Nagano Children's Hospital, Nagano, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawame
authors.affiliation: Department of Pediatrics, Central Hospital, Aichi Human Service Center, Aichi, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Mizuno
authors.affiliation: Division of Developmental Disability, Misakaenosono Mutsumi Developmental, Medical, and Welfare Center, Isahaya, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Kondoh
authors.affiliation: Department of Medical Genetics, CHU Vaudois, Lausanna, Switzerland.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Addor
authors.affiliation: Department of Medical Genetics, CHRU de Lille, Lille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Coeslier-Dieux
authors.affiliation: CH d'Arras, Arras, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vincent-Delorme
authors.affiliation: Department of Cardiovascular Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tabayashi
authors.affiliation: Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Aoki
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan.
authors.forename: Afag
authors.initials: A
authors.lastname: Guliyeva
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D006330:Heart Defects, Congenital / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000502:physiology; D009634:Noonan Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D010375:Pedigree; D020837:SOS1 Protein / Q000235:genetics*; D013577:Syndrome
chemical_list: D020837:SOS1 Protein