دورية أكاديمية
Germline gain-of-function mutations in SOS1 cause Noonan syndrome.
| العنوان: | Germline gain-of-function mutations in SOS1 cause Noonan syndrome. |
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| المؤلفون: | Roberts AE; Harvard Partners Center for Genetics and Genomics and Harvard Medical School, Boston, Massachusetts 02115, USA., Araki T, Swanson KD, Montgomery KT, Schiripo TA, Joshi VA, Li L, Yassin Y, Tamburino AM, Neel BG, Kucherlapati RS |
| المصدر: | Nature genetics [Nat Genet] 2007 Jan; Vol. 39 (1), pp. 70-4. Date of Electronic Publication: 2006 Dec 03. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print-Electronic Cited Medium: Print ISSN: 1061-4036 (Print) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Nature Pub. Co., c1992- |
| مواضيع طبية MeSH: | Germ-Line Mutation*, Noonan Syndrome/*genetics , SOS1 Protein/*genetics, Adolescent ; Adult ; Child ; Child, Preschool ; DNA Mutational Analysis ; Female ; Genetic Testing ; Humans ; Infant ; Intracellular Signaling Peptides and Proteins/genetics ; Male ; Models, Biological ; Models, Molecular ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; Protein Tyrosine Phosphatases/genetics ; SOS1 Protein/chemistry |
| مستخلص: | Noonan syndrome, the most common single-gene cause of congenital heart disease, is characterized by short stature, characteristic facies, learning problems and leukemia predisposition. Gain-of-function mutations in PTPN11, encoding the tyrosine phosphatase SHP2, cause approximately 50% of Noonan syndrome cases. SHP2 is required for RAS-ERK MAP kinase (MAPK) cascade activation, and Noonan syndrome mutants enhance ERK activation ex vivo and in mice. KRAS mutations account for <5% of cases of Noonan syndrome, but the gene(s) responsible for the remainder are unknown. We identified missense mutations in SOS1, which encodes an essential RAS guanine nucleotide-exchange factor (RAS-GEF), in approximately 20% of cases of Noonan syndrome without PTPN11 mutation. The prevalence of specific cardiac defects differs in SOS1 mutation-associated Noonan syndrome. Noonan syndrome-associated SOS1 mutations are hypermorphs encoding products that enhance RAS and ERK activation. Our results identify SOS1 mutants as a major cause of Noonan syndrome, representing the first example of activating GEF mutations associated with human disease and providing new insights into RAS-GEF regulation. |
| التعليقات: | Comment in: Nat Genet. 2007 Jan;39(1):8-9. (PMID: 17192780) |
| معلومات مُعتمدة: | DE16140 United States DE NIDCR NIH HHS; M01-RR02172 United States RR NCRR NIH HHS; R37CA49152 United States CA NCI NIH HHS |
| سلسلة جزيئية: | RefSeq NM_002834; NM_004333; NM_004383; NM_005633; NM_006939; NM_012219; NM_018440; NM_080549 |
| المشرفين على المادة: | 0 (Intracellular Signaling Peptides and Proteins) 0 (SOS1 Protein) EC 3.1.3.48 (PTPN11 protein, human) EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11) EC 3.1.3.48 (Protein Tyrosine Phosphatases) |
| تواريخ الأحداث: | Date Created: 20061205 Date Completed: 20070221 Latest Revision: 20220817 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1038/ng1926 |
| PMID: | 17143285 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1061-4036 |
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| DOI: | 10.1038/ng1926 |