Leopard syndrome pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
Molecular studies have shown that Leopard syndrome is caused by different missense mutations in [[PTPN11]] | Molecular studies have shown that Leopard syndrome is caused by different missense mutations in [[PTPN11]].<ref name="pmid16523510">{{cite journal| author=Digilio MC, Sarkozy A, de Zorzi A, Pacileo G, Limongelli G, Mingarelli R et al.| title=LEOPARD syndrome: clinical diagnosis in the first year of life. | journal=Am J Med Genet A | year= 2006 | volume= 140 | issue= 7 | pages= 740-6 | pmid=16523510 | doi=10.1002/ajmg.a.31156 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16523510 }} </ref> Mutations cause a loss of [[catalytic activity]] of the SHP2 protein, which is a previously unrecognized behavior for this class of mutations.<ref name="pmid16358218">{{cite journal| author=Tartaglia M, Martinelli S, Stella L, Bocchinfuso G, Flex E, Cordeddu V et al.| title=Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. | journal=Am J Hum Genet | year= 2006 | volume= 78 | issue= 2 | pages= 279-90 | pmid=16358218 | doi=10.1086/499925 | pmc=PMC1380235 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16358218 }} </ref> This interferes with growth factor and related signalling. | ||
==Pathophysiology== | ==Pathophysiology== | ||
In the two predominant mutations of Leopard syndrome, the mutations cause a loss of [[catalytic activity]] of the SHP2 protein(the gene product of the ''[[PTPN11]]'' gene), which is a previously unrecognized behavior for this class of mutations.<ref>{{cite journal |author=Tartaglia M, Martinelli S, Stella L, ''et al'' |title=Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease |journal=Am. J. Hum. Genet. |volume=78 |issue=2 |pages=279–90 |year=2006 |pmid=16358218 |doi=10.1086/499925}}</ref> This interferes with growth factor and related signalling. While further research confirms this mechanism,<ref>{{cite journal |author=Hanna N, Montagner A, Lee WH, ''et al'' |title=Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K binding on Gab1 |journal=FEBS Lett. |volume=580 |issue=10 |pages=2477–82 |year=2006 |pmid=16638574 |doi=10.1016/j.febslet.2006.03.088}}</ref><ref>{{cite journal |author=Kontaridis MI, Swanson KD, David FS, Barford D, Neel BG |title=PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects |journal=J. Biol. Chem. |volume=281 |issue=10 |pages=6785–92 |year=2006 |pmid=16377799 |doi=10.1074/jbc.M513068200|url=http://www.jbc.org/cgi/content/full/281/10/6785}}</ref> additional research is needed to determine how this relates to all of the observed effects of Leopard syndrome. | In the two predominant mutations of Leopard syndrome, the mutations cause a loss of [[catalytic activity]] of the SHP2 protein(the gene product of the ''[[PTPN11]]'' gene located at chromosome 12q22-qter), which is a previously unrecognized behavior for this class of mutations.<ref>{{cite journal |author=Tartaglia M, Martinelli S, Stella L, ''et al'' |title=Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease |journal=Am. J. Hum. Genet. |volume=78 |issue=2 |pages=279–90 |year=2006 |pmid=16358218 |doi=10.1086/499925}}</ref> This interferes with growth factor and related signalling. While further research confirms this mechanism,<ref>{{cite journal |author=Hanna N, Montagner A, Lee WH, ''et al'' |title=Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K binding on Gab1 |journal=FEBS Lett. |volume=580 |issue=10 |pages=2477–82 |year=2006 |pmid=16638574 |doi=10.1016/j.febslet.2006.03.088}}</ref><ref>{{cite journal |author=Kontaridis MI, Swanson KD, David FS, Barford D, Neel BG |title=PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects |journal=J. Biol. Chem. |volume=281 |issue=10 |pages=6785–92 |year=2006 |pmid=16377799 |doi=10.1074/jbc.M513068200|url=http://www.jbc.org/cgi/content/full/281/10/6785}}</ref> additional research is needed to determine how this relates to all of the observed effects of Leopard syndrome. | ||
==References== | ==References== | ||
Revision as of 16:21, 6 September 2013
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamed Moubarak, M.D. [2]
Overview
Molecular studies have shown that Leopard syndrome is caused by different missense mutations in PTPN11.[1] Mutations cause a loss of catalytic activity of the SHP2 protein, which is a previously unrecognized behavior for this class of mutations.[2] This interferes with growth factor and related signalling.
Pathophysiology
In the two predominant mutations of Leopard syndrome, the mutations cause a loss of catalytic activity of the SHP2 protein(the gene product of the PTPN11 gene located at chromosome 12q22-qter), which is a previously unrecognized behavior for this class of mutations.[3] This interferes with growth factor and related signalling. While further research confirms this mechanism,[4][5] additional research is needed to determine how this relates to all of the observed effects of Leopard syndrome.
References
- ↑ Digilio MC, Sarkozy A, de Zorzi A, Pacileo G, Limongelli G, Mingarelli R; et al. (2006). "LEOPARD syndrome: clinical diagnosis in the first year of life". Am J Med Genet A. 140 (7): 740–6. doi:10.1002/ajmg.a.31156. PMID 16523510.
- ↑ Tartaglia M, Martinelli S, Stella L, Bocchinfuso G, Flex E, Cordeddu V; et al. (2006). "Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease". Am J Hum Genet. 78 (2): 279–90. doi:10.1086/499925. PMC 1380235. PMID 16358218.
- ↑ Tartaglia M, Martinelli S, Stella L; et al. (2006). "Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease". Am. J. Hum. Genet. 78 (2): 279–90. doi:10.1086/499925. PMID 16358218.
- ↑ Hanna N, Montagner A, Lee WH; et al. (2006). "Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K binding on Gab1". FEBS Lett. 580 (10): 2477–82. doi:10.1016/j.febslet.2006.03.088. PMID 16638574.
- ↑ Kontaridis MI, Swanson KD, David FS, Barford D, Neel BG (2006). "PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects". J. Biol. Chem. 281 (10): 6785–92. doi:10.1074/jbc.M513068200. PMID 16377799.