Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome.
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.
Narumi
Yoko
Y
Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan.
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
Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan.
Sakurai
Masahiro
M
Department of Cardiovascular Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
Cavé
Hélène
H
Department of Genetics, Hôpital Robert Debré (APHP), Paris, France.
Verloes
Alain
A
Department of Genetics, Hôpital Robert Debré (APHP), Paris, France.
Nishio
Kimio
K
Department of Clinical Genetics, Seirei Hamamatsu General Hospital, Hamamatsu, Japan.|Nishio Family Clinic, Hamamatsu, Japan.
Ohashi
Hirofumi
H
Division of Medical Genetics, Saitama Children's Medical Center, Saitama, Japan.
Kurosawa
Kenji
K
Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan.
Okamoto
Nobuhiko
N
Department of Planning and Research, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
Kawame
Hiroshi
H
Division of Medical Genetics, Nagano Children's Hospital, Nagano, Japan.
Mizuno
Seiji
S
Department of Pediatrics, Central Hospital, Aichi Human Service Center, Aichi, Japan.
Kondoh
Tatsuro
T
Division of Developmental Disability, Misakaenosono Mutsumi Developmental, Medical, and Welfare Center, Isahaya, Japan.
Addor
Marie-Claude
MC
Department of Medical Genetics, CHU Vaudois, Lausanna, Switzerland.
Coeslier-Dieux
Anne
A
Department of Medical Genetics, CHRU de Lille, Lille, France.
Vincent-Delorme
Catherine
C
CH d'Arras, Arras, France.
Tabayashi
Koichi
K
Department of Cardiovascular Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
Aoki
Masashi
M
Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Kobayashi
Tomoko
T
Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan.
Guliyeva
Afag
A
Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan.
Kure
Shigeo
S
Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan.
Matsubara
Yoichi
Y
Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, 980-8574, Japan.
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
D020837:SOS1 Protein