Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome.

Details

Serval ID
serval:BIB_250C81F9A4DD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome.
Journal
Journal of Human Genetics
Author(s)
Narumi Y., Aoki Y., Niihori T., Sakurai M., Cavé H., Verloes A., Nishio K., Ohashi H., Kurosawa K., Okamoto N., Kawame H., Mizuno S., Kondoh T., Addor M.C., Coeslier-Dieux A., Vincent-Delorme C., Tabayashi K., Aoki M., Kobayashi T., Guliyeva A., Kure S., Matsubara Y.
ISSN
1434-5161
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
53
Number
9
Pages
834-841
Language
english
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.
Keywords
Abnormalities, Multiple, Adult, Child, Child, Preschool, DNA Mutational Analysis, Family, Female, Heart Defects, Congenital, Humans, Infant, Male, Mutation, Noonan Syndrome, Pedigree, SOS1 Protein, Syndrome
Pubmed
Web of science
Open Access
Yes
Create date
31/03/2009 10:56
Last modification date
20/08/2019 13:03
Usage data