LIVIVO - Search results -

Search results

Result 1 - 10 of total 22

Search options

Article ; Online: Juvenile xanthogranuloma in Noonan syndrome.

Ali, Marwan M / Gilliam, Amy E / Ruben, Beth S / Tidyman, William E / Rauen, Katherine A

American journal of medical genetics. Part A

2021 Volume 185, Issue 10, Page(s) 3048–3052

Abstract: Noonan syndrome (NS) is one of the common RASopathies. While the clinical phenotype in NS is variable, it is typically characterized by distinctive craniofacial features, cardiac defects, reduced growth, bleeding disorders, learning issues, and an ... ...

Abstract	Noonan syndrome (NS) is one of the common RASopathies. While the clinical phenotype in NS is variable, it is typically characterized by distinctive craniofacial features, cardiac defects, reduced growth, bleeding disorders, learning issues, and an increased risk of cancer. Several different genes cause NS, all of which are involved in the Ras/mitogen-activated protein kinase (Ras/MAPK) pathway. Juvenile xanthogranuloma (JXG) is an uncommon, proliferative, self-limited cutaneous disorder that affects young individuals and may be overlooked or misdiagnosed due to its transient nature. A RASopathy that is known to be associated with JXG is neurofibromatosis type 1 (NF1). JXG in NF1 has also been reported in association with a juvenile myelomonocytic leukemia (JMML). As RASopathies, both NS and NF1 have an increased incidence of JMML. We report a 10-month-old female with NS who has a PTPN11 pathogenic variant resulting in a heterozygous SHP2 p.Y62D missense mutation. She was found to have numerous, small, yellow-pink smooth papules that were histopathologically confirmed to be JXG. In understanding the common underlying pathogenetic dysregulation of the Ras/MAPK pathway in both NS and NF1, this report suggests a possible molecular association for why NS individuals may be predisposed to JXG.
MeSH term(s)	Female ; Genetic Predisposition to Disease ; Humans ; Infant ; Leukemia, Myelomonocytic, Juvenile/complications ; Leukemia, Myelomonocytic, Juvenile/genetics ; Leukemia, Myelomonocytic, Juvenile/pathology ; Mutation, Missense/genetics ; Neurofibromin 1/genetics ; Noonan Syndrome/complications ; Noonan Syndrome/genetics ; Noonan Syndrome/pathology ; Phenotype ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics ; Xanthogranuloma, Juvenile/complications ; Xanthogranuloma, Juvenile/genetics ; Xanthogranuloma, Juvenile/pathology ; ras Proteins/genetics
Chemical Substances	NF1 protein, human ; Neurofibromin 1 ; PTPN11 protein, human (EC 3.1.3.48) ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 (EC 3.1.3.48) ; ras Proteins (EC 3.6.5.2)
Language	English
Publishing date	2021-05-25
Publishing country	United States
Document type	Case Reports ; Research Support, N.I.H., Extramural
ZDB-ID	2108614-X
ISSN	1552-4833 ; 0148-7299 ; 1552-4825
ISSN (online)	1552-4833
ISSN	0148-7299 ; 1552-4825
DOI	10.1002/ajmg.a.62353
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1376/A: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article ; Online: Familial cardio-facio-cutaneous syndrome: Vertical transmission of the BRAF p.G464R pathogenic variant and review of the literature.

Rauen, Katherine A / Maeda, Yoshiko / Egense, Alena / Tidyman, William E

American journal of medical genetics. Part A

2020 Volume 185, Issue 2, Page(s) 469–475

Abstract: Cardio-facio-cutaneous syndrome (CFC) is one of the RASopathies and is caused by germline mutations that activate the Ras/mitogen-activated protein kinase (MAPK) pathway. CFC is due to heterozygous germline mutations in protein kinases BRAF, MEK1, or ... ...

Abstract	Cardio-facio-cutaneous syndrome (CFC) is one of the RASopathies and is caused by germline mutations that activate the Ras/mitogen-activated protein kinase (MAPK) pathway. CFC is due to heterozygous germline mutations in protein kinases BRAF, MEK1, or MEK2 and rarely in KRAS, a small GTPase. CFC is a multiple congenital anomaly disorder in which individuals may have craniofacial dysmorphia, heart issues, skin and hair anomalies, and delayed development. Pathogenic variants for CFC syndrome are usually considered de novo because vertical transmission has only been reported with MEK2 and KRAS. The index case was a 3-year-old male with features consistent with the clinical diagnosis of CFC. Sequencing revealed a previously reported heterozygous likely pathogenic variant BRAF p.G464R. Upon detailed family history, the index case's pregnant mother was noted to have similar features to her son. Targeted familial testing of the BRAF pathogenic variant was performed on the mother, confirming her diagnosis. Prenatal genetic testing for the fetus was declined, but postnatal molecular testing of the index case's sister was positive for the familial BRAF p.G464R variant. Functional analysis of the variant demonstrated increased kinase activity. We report the first identified vertically transmitted functional BRAF pathogenic variant. Our findings emphasize the importance of obtaining a comprehensive evaluation of family members and that activating pathogenic variants within the canonical MAPK cascade mediated by BRAF are compatible with human reproduction.
MeSH term(s)	Abnormalities, Multiple/genetics ; Abnormalities, Multiple/pathology ; Adult ; Child, Preschool ; Ectodermal Dysplasia/genetics ; Ectodermal Dysplasia/pathology ; Facies ; Failure to Thrive/genetics ; Failure to Thrive/pathology ; Female ; Genetic Predisposition to Disease ; Germ-Line Mutation/genetics ; Heart Defects, Congenital/genetics ; Heart Defects, Congenital/pathology ; Humans ; MAP Kinase Kinase 1/genetics ; MAP Kinase Kinase 2/genetics ; Male ; Pregnancy ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins p21(ras)/genetics
Chemical Substances	KRAS protein, human ; MAP2K2 protein, human (EC 2.7.1.-) ; BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; MAP Kinase Kinase 1 (EC 2.7.12.2) ; MAP Kinase Kinase 2 (EC 2.7.12.2) ; MAP2K1 protein, human (EC 2.7.12.2) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
Language	English
Publishing date	2020-12-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2108614-X
ISSN	1552-4833 ; 0148-7299 ; 1552-4825
ISSN (online)	1552-4833
ISSN	0148-7299 ; 1552-4825
DOI	10.1002/ajmg.a.61995
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1376/A: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Expansion of the RASopathies.

Tidyman, William E / Rauen, Katherine A

Current genetic medicine reports

2016 Volume 4, Issue 3, Page(s) 57–64

Abstract: The Ras/mitogen activated protein kinase (MAPK) pathway is essential in the regulation of cell cycle, differentiation, growth, cell senescence and apoptosis, all of which are critical to normal development. A class of neurodevelopmental disorders, ... ...

Abstract	The Ras/mitogen activated protein kinase (MAPK) pathway is essential in the regulation of cell cycle, differentiation, growth, cell senescence and apoptosis, all of which are critical to normal development. A class of neurodevelopmental disorders, RASopathies, is caused by germline mutations in genes of the Ras/MAPK pathway. Through the use of whole exome sequencing and targeted sequencing of selected genes in cohorts of panel-negative RASopathy patients, several new genes have been identified. These include:
Language	English
Publishing date	2016-07-01
Publishing country	United States
Document type	Journal Article
ISSN	2167-4876
ISSN	2167-4876
DOI	10.1007/s40142-016-0100-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- Full text online
- Order with fees

Article ; Online: Pathogenetics of the RASopathies.

Tidyman, William E / Rauen, Katherine A

Human molecular genetics

2016 Volume 25, Issue R2, Page(s) R123–R132

Abstract: The RASopathies are defined as a group of medical genetics syndromes that are caused by germ-line mutations in genes that encode components or regulators of the Ras/mitogen-activated protein kinase (MAPK) pathway. Taken together, the RASopathies ... ...

Abstract	The RASopathies are defined as a group of medical genetics syndromes that are caused by germ-line mutations in genes that encode components or regulators of the Ras/mitogen-activated protein kinase (MAPK) pathway. Taken together, the RASopathies represent one of the most prevalent groups of malformation syndromes affecting greater than 1 in 1,000 individuals. The Ras/MAPK pathway has been well studied in the context of cancer as it plays essential roles in growth, differentiation, cell cycle, senescence and apoptosis, all of which are also critical to normal development. The consequence of germ-line dysregulation leads to phenotypic alterations of development. RASopathies can be caused by several pathogenetic mechanisms that ultimately impact or alter the normal function and regulation of the MAPK pathway. These pathogenetic mechanisms can include functional alteration of GTPases, Ras GTPase-activating proteins, Ras guanine exchange factors, kinases, scaffolding or adaptor proteins, ubiquitin ligases, phosphatases and pathway inhibitors. Although these mechanisms are diverse, the common underlying biochemical phenotype shared by all the RASopathies is Ras/MAPK pathway activation. This results in the overlapping phenotypic features among these syndromes.
Language	English
Publishing date	2016-07-12
Publishing country	England
Document type	Journal Article
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddw191
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3469: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: MEK-inhibitor-mediated rescue of skeletal myopathy caused by activating Hras mutation in a Costello syndrome mouse model.

Tidyman, William E / Goodwin, Alice F / Maeda, Yoshiko / Klein, Ophir D / Rauen, Katherine A

Disease models & mechanisms

2021 Volume 15, Issue 2

Abstract: Costello syndrome (CS) is a congenital disorder caused by heterozygous activating germline HRAS mutations in the canonical Ras/mitogen-activated protein kinase (Ras/MAPK) pathway. CS is one of the RASopathies, a large group of syndromes caused by ... ...

Abstract	Costello syndrome (CS) is a congenital disorder caused by heterozygous activating germline HRAS mutations in the canonical Ras/mitogen-activated protein kinase (Ras/MAPK) pathway. CS is one of the RASopathies, a large group of syndromes caused by mutations within various components of the Ras/MAPK pathway. An important part of the phenotype that greatly impacts quality of life is hypotonia. To gain a better understanding of the mechanisms underlying hypotonia in CS, a mouse model with an activating HrasG12V allele was utilized. We identified a skeletal myopathy that was due, in part, to inhibition of embryonic myogenesis and myofiber formation, resulting in a reduction in myofiber size and number that led to reduced muscle mass and strength. In addition to hyperactivation of the Ras/MAPK and PI3K/AKT pathways, there was a significant reduction in p38 signaling, as well as global transcriptional alterations consistent with the myopathic phenotype. Inhibition of Ras/MAPK pathway signaling using a MEK inhibitor rescued the HrasG12V myopathy phenotype both in vitro and in vivo, demonstrating that increased MAPK signaling is the main cause of the muscle phenotype in CS.
MeSH term(s)	Animals ; Costello Syndrome/genetics ; Costello Syndrome/metabolism ; Mice ; Mitogen-Activated Protein Kinase Kinases/genetics ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Muscular Diseases ; Mutation/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins p21(ras)/genetics ; Proto-Oncogene Proteins p21(ras)/metabolism ; Quality of Life
Chemical Substances	Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; Hras protein, mouse (EC 3.6.5.2) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
Language	English
Publishing date	2021-11-19
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2451104-3
ISSN	1754-8411 ; 1754-8403
ISSN (online)	1754-8411
ISSN	1754-8403
DOI	10.1242/dmm.049166
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Ras/MAPK dysregulation in development causes a skeletal myopathy in an activating Braf

Maeda, Yoshiko / Tidyman, William E / Ander, Bradley P / Pritchard, Catrin A / Rauen, Katherine A

Developmental dynamics : an official publication of the American Association of Anatomists

2021 Volume 250, Issue 8, Page(s) 1074–1095

Abstract: Background: Cardio-facio-cutaneous (CFC) syndrome is a human multiple congenital anomaly syndrome that is caused by activating heterozygous mutations in either BRAF, MEK1, or MEK2, three protein kinases of the Ras/mitogen-activated protein kinase (MAPK) ...

Abstract	Background: Cardio-facio-cutaneous (CFC) syndrome is a human multiple congenital anomaly syndrome that is caused by activating heterozygous mutations in either BRAF, MEK1, or MEK2, three protein kinases of the Ras/mitogen-activated protein kinase (MAPK) pathway. CFC belongs to a group of syndromes known as RASopathies. Skeletal muscle hypotonia is a ubiquitous phenotype of RASopathies, especially in CFC syndrome. To better understand the underlying mechanisms for the skeletal myopathy in CFC, a mouse model with an activating Braf Results: The activating Braf Conclusions: A skeletal myopathy was identified in the CFC Braf
MeSH term(s)	Alleles ; Animals ; Ectodermal Dysplasia/genetics ; Ectodermal Dysplasia/metabolism ; Ectodermal Dysplasia/pathology ; Facies ; Failure to Thrive/genetics ; Failure to Thrive/metabolism ; Failure to Thrive/pathology ; Heart Defects, Congenital/genetics ; Heart Defects, Congenital/metabolism ; Heart Defects, Congenital/pathology ; Mice ; Mitogen-Activated Protein Kinases/genetics ; Mitogen-Activated Protein Kinases/metabolism ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/pathology ; Muscular Diseases/genetics ; Muscular Diseases/metabolism ; Muscular Diseases/pathology ; Phenotype ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins B-raf/metabolism
Chemical Substances	Braf protein, mouse (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2021-02-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1102541-4
ISSN	1097-0177 ; 1058-8388
ISSN (online)	1097-0177
ISSN	1058-8388
DOI	10.1002/dvdy.309
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Ub I Zs.60: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 64: Show issues

Order via subito

Details ▾

Article ; Online: MEK-inhibitor-mediated rescue of skeletal myopathy caused by activating Hras mutation in a Costello syndrome mouse model

William E. Tidyman / Alice F. Goodwin / Yoshiko Maeda / Ophir D. Klein / Katherine A. Rauen

Disease Models & Mechanisms, Vol 15, Iss

2022 Volume 2

Abstract	Costello syndrome (CS) is a congenital disorder caused by heterozygous activating germline HRAS mutations in the canonical Ras/mitogen-activated protein kinase (Ras/MAPK) pathway. CS is one of the RASopathies, a large group of syndromes caused by mutations within various components of the Ras/MAPK pathway. An important part of the phenotype that greatly impacts quality of life is hypotonia. To gain a better understanding of the mechanisms underlying hypotonia in CS, a mouse model with an activating HrasG12V allele was utilized. We identified a skeletal myopathy that was due, in part, to inhibition of embryonic myogenesis and myofiber formation, resulting in a reduction in myofiber size and number that led to reduced muscle mass and strength. In addition to hyperactivation of the Ras/MAPK and PI3K/AKT pathways, there was a significant reduction in p38 signaling, as well as global transcriptional alterations consistent with the myopathic phenotype. Inhibition of Ras/MAPK pathway signaling using a MEK inhibitor rescued the HrasG12V myopathy phenotype both in vitro and in vivo, demonstrating that increased MAPK signaling is the main cause of the muscle phenotype in CS.
Keywords	costello syndrome ; hypotonia ; mek inhibitor ; myogenesis ; rasopathies ; ras/mapk ; Medicine ; R ; Pathology ; RB1-214
Subject code	570
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	The Company of Biologists
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Mutational and functional analysis in human Ras/MAP kinase genetic syndromes.

Tidyman, William E / Rauen, Katherine A

Methods in molecular biology (Clifton, N.J.)

2010 Volume 661, Page(s) 433–447

Abstract: The Ras/mitogen-activated protein kinase (MAPK) pathway is essential in regulation of the cell cycle, cell differentiation, growth, and cell senescence, each of which are critical to normal development. A class of developmental disorders, the " ... ...

Abstract	The Ras/mitogen-activated protein kinase (MAPK) pathway is essential in regulation of the cell cycle, cell differentiation, growth, and cell senescence, each of which are critical to normal development. A class of developmental disorders, the "RASopathies," is caused by germline mutations in genes that encode protein components of the Ras/MAPK pathway which result in dysregulation of the pathway and profound deleterious effects on development. One of these syndromes, cardiofaciocutaneous (CFC) syndrome, is caused by germline mutations in BRAF, MAP2K1 (MEK1) and MAP2K2 (MEK2), and possibly KRAS genes. Here, we describe the laboratory protocols and methods that we used to identify mutations in BRAF and MEK1/2 genes as causative for CFC syndrome. In addition, we present the techniques used to determine the effect these mutations have on activity of the Ras/MAPK pathway through Western blot analysis of the phosphorylation of endogenous ERK1/2, as well as through the use of an in vitro kinase assay that measures the phosphorylation of Elk-1.
MeSH term(s)	Base Sequence ; Blotting, Western ; Cloning, Molecular ; DNA/genetics ; DNA/isolation & purification ; DNA Mutational Analysis/methods ; DNA, Complementary/genetics ; Ectodermal Dysplasia/enzymology ; Ectodermal Dysplasia/genetics ; Ectodermal Dysplasia/metabolism ; Enzyme Assays/methods ; Facies ; Failure to Thrive/enzymology ; Failure to Thrive/genetics ; Failure to Thrive/metabolism ; Genome/genetics ; HEK293 Cells ; Heart Defects, Congenital/enzymology ; Heart Defects, Congenital/genetics ; Heart Defects, Congenital/metabolism ; Humans ; MAP Kinase Kinase 1/genetics ; MAP Kinase Kinase 1/metabolism ; MAP Kinase Kinase 2/genetics ; MAP Kinase Kinase 2/metabolism ; MAP Kinase Signaling System ; Point Mutation ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins B-raf/metabolism ; Syndrome ; Transfection
Chemical Substances	DNA, Complementary ; DNA (9007-49-2) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; MAP Kinase Kinase 1 (EC 2.7.12.2) ; MAP Kinase Kinase 2 (EC 2.7.12.2)
Language	English
Publishing date	2010
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-60761-795-2_27
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- Full text online
- Order with fees

Article ; Online: The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation.

Tidyman, William E / Rauen, Katherine A

Current opinion in genetics & development

2009 Volume 19, Issue 3, Page(s) 230–236

Abstract: The Ras/mitogen activated protein kinase (MAPK) pathway is essential in the regulation of the cell cycle, differentiation, growth and cell senescence, all of which are critical to normal development. It is therefore not surprising that its dysregulation ... ...

Abstract	The Ras/mitogen activated protein kinase (MAPK) pathway is essential in the regulation of the cell cycle, differentiation, growth and cell senescence, all of which are critical to normal development. It is therefore not surprising that its dysregulation has profound effects on development. A class of developmental syndromes, the 'RASopathies', is caused by germline mutations in genes that encode protein components of the Ras/MAPK pathway. The vast majority of these mutations result in increased signal transduction down the Ras/MAPK pathway, but usually to a lesser extent than somatic mutations associated with oncogenesis. Each syndrome exhibits unique phenotypic features, however, since they all cause dysregulation of the Ras/MAPK pathway, there are numerous overlapping phenotypic features between the syndromes, including characteristic facial features, cardiac defects, cutaneous abnormalities, neurocognitive delay and a predisposition to malignancies. Here we review the clinical and underlying molecular basis for each of these syndromes.
MeSH term(s)	Animals ; Germ-Line Mutation ; Humans ; Mitogen-Activated Protein Kinases/genetics ; Mitogen-Activated Protein Kinases/metabolism ; Models, Biological ; Noonan Syndrome/genetics ; Noonan Syndrome/pathology ; Noonan Syndrome/physiopathology ; SOS1 Protein/genetics ; SOS1 Protein/metabolism ; Signal Transduction/genetics ; Signal Transduction/physiology ; Syndrome ; ras Proteins/genetics ; ras Proteins/metabolism
Chemical Substances	SOS1 Protein ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; ras Proteins (EC 3.6.5.2)
Language	English
Publishing date	2009-05-19
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1077312-5
ISSN	1879-0380 ; 0959-437X
ISSN (online)	1879-0380
ISSN	0959-437X
DOI	10.1016/j.gde.2009.04.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3240: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Noonan, Costello and cardio-facio-cutaneous syndromes: dysregulation of the Ras-MAPK pathway.

Tidyman, William E / Rauen, Katherine A

Expert reviews in molecular medicine

2008 Volume 10, Page(s) e37

Abstract: A class of developmental disorders caused by dysregulation of the Ras-induced mitogen-activated protein kinase (MAPK) cascade (the Ras-MAPK pathway) has emerged. Three of these disorders - Noonan, Costello and cardio-facio-cutaneous syndromes - have ... ...

Abstract	A class of developmental disorders caused by dysregulation of the Ras-induced mitogen-activated protein kinase (MAPK) cascade (the Ras-MAPK pathway) has emerged. Three of these disorders - Noonan, Costello and cardio-facio-cutaneous syndromes - have overlapping phenotypic features characterised by distinctive facial dysmorphia, cardiac defects, musculoskeletal and cutaneous abnormalities, and neurocognitive delay. The germline mutations associated with these disorders are in genes that encode proteins of the Ras-MAPK pathway. In vitro studies have determined that the overwhelming majority of these mutations result in increased signal transduction down the pathway, but usually to a lesser degree than somatic mutations in the same genes that are associated with cancer. The Ras-MAPK pathway is essential in the regulation of the cell cycle, differentiation, growth and senescence, so it is not surprising that germline mutations that affect its function have profound effects on development. Here we review the clinical consequences of the known molecular lesions associated with Noonan syndrome, Costello syndrome and cardio-facio-cutaneous syndrome, and explore possible therapeutic modalities for treatment.
MeSH term(s)	Abnormalities, Multiple/genetics ; Abnormalities, Multiple/metabolism ; Abnormalities, Multiple/pathology ; Animals ; Craniofacial Abnormalities/genetics ; Craniofacial Abnormalities/metabolism ; Genes, ras ; Heart Defects, Congenital/genetics ; Heart Defects, Congenital/metabolism ; Humans ; LEOPARD Syndrome/genetics ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinases/genetics ; Mitogen-Activated Protein Kinases/metabolism ; Mutation ; Noonan Syndrome/genetics ; Noonan Syndrome/metabolism ; Noonan Syndrome/pathology ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins B-raf/metabolism ; Proto-Oncogene Proteins c-raf/genetics ; Proto-Oncogene Proteins c-raf/metabolism ; Proto-Oncogene Proteins p21(ras)/genetics ; Proto-Oncogene Proteins p21(ras)/metabolism ; SOS1 Protein/genetics ; SOS1 Protein/metabolism ; Syndrome ; ras Proteins/genetics ; ras Proteins/metabolism
Chemical Substances	KRAS protein, human ; Proto-Oncogene Proteins ; SOS1 Protein ; BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Proto-Oncogene Proteins c-raf (EC 2.7.11.1) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; PTPN11 protein, human (EC 3.1.3.48) ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 (EC 3.1.3.48) ; HRAS protein, human (EC 3.6.5.2) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; ras Proteins (EC 3.6.5.2)
Language	English
Publishing date	2008-12-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ISSN	1462-3994
ISSN (online)	1462-3994
DOI	10.1017/S1462399408000902
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED