SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome
Background: Heterozygous gain-of-function mutations in various genes encoding proteins of the Ras-MAPK signalling cascade have been identified as the genetic basis of Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS). Mutations of SOS1, the gene encoding a guanine nucleotide exchange f...
Saved in:
Published in | Journal of medical genetics Vol. 44; no. 10; pp. 651 - 656 |
---|---|
Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
BMJ Publishing Group Ltd
01.10.2007
BMJ BMJ Publishing Group LTD BMJ Group |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Background: Heterozygous gain-of-function mutations in various genes encoding proteins of the Ras-MAPK signalling cascade have been identified as the genetic basis of Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS). Mutations of SOS1, the gene encoding a guanine nucleotide exchange factor for Ras, have been the most recent discoveries in patients with NS, but this gene has not been studied in patients with CFCS. Methods and results: We investigated SOS1 in a large cohort of patients with disorders of the NS–CFCS spectrum, who had previously tested negative for mutations in PTPN11, KRAS, BRAF, MEK1 and MEK2. Missense mutations of SOS1 were discovered in 28% of patients with NS. In contrast, none of the patients classified as having CFCS was found to carry a pathogenic sequence change in this gene. Conclusion: We have confirmed SOS1 as the second major gene for NS. Patients carrying mutations in this gene have a distinctive phenotype with frequent ectodermal anomalies such as keratosis pilaris and curly hair. However, the clinical picture associated with SOS1 mutations is different from that of CFCS. These findings corroborate that, despite being caused by gain-of-function mutations in molecules belonging to the same pathway, NS and CFCS scarcely overlap genotypically. |
---|---|
Bibliography: | ark:/67375/NVC-H1LR2CK3-G PMID:17586837 href:jmedgenet-44-651.pdf Correspondence to: Martin Zenker MD, Institute of Human Genetics, University of Erlangen-Nuremberg, Schwabachanlage 10, 91054 Erlangen, Germany; mzenker@humgenet.uni-erlangen.de local:0440651 istex:11873B39D8F919DF6FEAB4D18290338BA24A468D ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 SourceType-Other Sources-1 ObjectType-Article-2 content type line 63 ObjectType-Correspondence-1 |
ISSN: | 0022-2593 1468-6244 1468-6244 |
DOI: | 10.1136/jmg.2007.051276 |