Germline mutations in HRAS proto-oncogene cause Costello syndrome.
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.
Aoki
Yoko
Y
Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai 980-8574, Japan. aokiy@mail.tains.tohoku.ac.jp
Niihori
Tetsuya
T
Kawame
Hiroshi
H
Kurosawa
Kenji
K
Ohashi
Hirofumi
H
Tanaka
Yukichi
Y
Filocamo
Mirella
M
Kato
Kumi
K
Suzuki
Yoichi
Y
Kure
Shigeo
S
Matsubara
Yoichi
Y
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
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)