Noonan syndrome causes: Difference between revisions
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| {{OMIM2|163950}} | | {{OMIM2|163950}} | ||
| [[PTPN11]] | | [[PTPN11]] | ||
| In most of the families with multiple affected members, NS maps to [[Chromosome 12 (human)|chromosome 12]]q24.1. In 2001, it was reported that approximately half of a group of patients with Noonan syndrome carried a mutation of the ''PTPN11'' gene at that location, which encodes protein tyrosine phosphatase SHP-2.<ref>{{cite journal |author=Tartaglia M, Mehler EL, Goldberg R, ''et al'' |title=Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome |journal=Nat. Genet. |volume=29 |issue=4 |pages=465–8 |year=2001|pmid=11704759 |doi=10.1038/ng772}} | | In most of the families with multiple affected members, NS maps to [[Chromosome 12 (human)|chromosome 12]]q24.1. In 2001, it was reported that approximately half of a group of patients with Noonan syndrome carried a mutation of the ''PTPN11'' gene at that location, which encodes protein tyrosine phosphatase SHP-2.<ref>{{cite journal |author=Tartaglia M, Mehler EL, Goldberg R, ''et al'' |title=Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome |journal=Nat. Genet. |volume=29 |issue=4 |pages=465–8 |year=2001|pmid=11704759 |doi=10.1038/ng772}}</ref> | ||
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Revision as of 21:56, 7 November 2013
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Causes
Recurrence in siblings and apparent transmission from parent to child has long suggested a genetic defect with autosomal dominantinheritance and variable expression. Mutations in the Ras/MAPK signaling pathways are known to be responsible for ~70% of NS cases.[1]
A person with NS has up to a 50% chance of transmitting it to a child. The fact that an affected parent is not always identified for children with NS suggests several possibilities:
- manifestations are variably expressed and could be so subtle as to go unrecognized (variable xpressivity), or
- a high proportion of cases represent new, sporadic mutations, or
- Noonan syndrome is heterogeneous, comprising more than one similar condition of differing cause, some not inherited.
| Type | OMIM | Gene | Description |
|---|---|---|---|
| NS1 | 163950 | PTPN11 | In most of the families with multiple affected members, NS maps to chromosome 12q24.1. In 2001, it was reported that approximately half of a group of patients with Noonan syndrome carried a mutation of the PTPN11 gene at that location, which encodes protein tyrosine phosphatase SHP-2.[2] |
| NS2 | 605275 | unknown (autosomal recessive)[3] | |
| NS3 | 609942 | KRAS | Additional mutations in KRAS [4] genes have been reported to cause Noonan syndrome in a smaller percentage of individuals with the syndrome. |
| NS4 | 610733 | SOS1 | It has recently been shown that activating mutations in SOS1 also give rise to NS.[5] Shp2 and SOS1 both have roles as positive regulators of the Ras/MAP kinase pathway suggesting that dysregulation of this pathway may play a major role in the genesis of this syndrome.[6] |
| NS5 | 611553 | RAF1 | Additional mutations in RAF1[7] genes have been reported to cause Noonan syndrome in a smaller percentage of individuals with the syndrome. |
References
- ↑ Razzaque MA, Komoike Y, Nishizawa T, Inai K, Furutani M, Higashinakagawa T, Matsuoka R (2012) Characterization of a novel KRAS mutation identified in Noonan syndrome. Am J Med Genet Adoi:10.1002/ajmg.a.34419.
- ↑ Tartaglia M, Mehler EL, Goldberg R; et al. (2001). "Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome". Nat. Genet. 29 (4): 465–8. doi:10.1038/ng772. PMID 11704759.
- ↑ PMID 10982482 (PMID 10982482)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand - ↑ Schubbert S, Zenker M, Rowe SL; et al. (2006). "Germline KRAS mutations cause Noonan syndrome". Nat. Genet. 38 (3): 331–6. doi:10.1038/ng1748. PMID 16474405.
- ↑ Roberts AE, Araki T, Swanson KD; et al. (2007). "Germline gain-of-function mutations in SOS1 cause Noonan syndrome". Nat. Genet. 39 (1): 70–4. doi:10.1038/ng1926. PMID 17143285.
- ↑ Bentires-Alj M, Kontaridis MI, Neel BG (2006). "Stops along the RAS pathway in human genetic disease". Nat. Med. 12 (3): 283–5. doi:10.1038/nm0306-283. PMID 16520774.
- ↑ Razzaque MA, Nishizawa T, Komoike Y; et al. (2007). "Germline gain-of-function mutations in RAF1 cause Noonan syndrome". Nat. Genet. 39 (8): 1013–7. doi:10.1038/ng2078. PMID 17603482.