title: Germline mutations in HRAS proto-oncogene cause Costello syndrome.
abstract: Costello syndrome is a multiple congenital anomaly and mental retardation syndrome characterized by coarse face, loose skin, cardiomyopathy and predisposition to tumors. We identified four heterozygous de novo mutations of HRAS in 12 of 13 affected individuals, all of which were previously reported as somatic and oncogenic mutations in various tumors. Our observations suggest that germline mutations in HRAS perturb human development and increase susceptibility to tumors.
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.forename: Tetsuya
authors.initials: T
authors.lastname: Niihori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawame
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohashi
authors.forename: Yukichi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Mirella
authors.initials: M
authors.lastname: Filocamo
authors.forename: Kumi
authors.initials: K
authors.lastname: Kato
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D009202:Cardiomyopathies / Q000235:genetics; D005145:Face / Q000002:abnormalities; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics; D000090063:Proto-Oncogene Mas; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012868:Skin Abnormalities / Q000235:genetics; D013577:Syndrome
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)